Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001371596.2(MFSD8):c.435A>C(p.Gly145Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
MFSD8 (HGNC:28486): (major facilitator superfamily domain containing 8) This gene encodes a ubiquitous integral membrane protein that contains a transporter domain and a major facilitator superfamily (MFS) domain. Other members of the major facilitator superfamily transport small solutes through chemiosmotic ion gradients. The substrate transported by this protein is unknown. The protein likely localizes to lysosomal membranes. Mutations in this gene are correlated with a variant form of late infantile-onset neuronal ceroid lipofuscinoses (vLINCL). [provided by RefSeq, Oct 2008]
MFSD8 Gene-Disease associations (from GenCC):
neuronal ceroid lipofuscinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
neuronal ceroid lipofuscinosis 7
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P
macular dystrophy with central cone involvement
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Our verdict: Benign. The variant received -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 4-127943756-T-G is Benign according to our data. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-127943756-T-G is described in CliVar as Likely_benign. Clinvar id is 380256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.28 with no splicing effect.
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Inborn genetic diseasesBenign:1
Sep 21, 2018
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Neuronal ceroid lipofuscinosis 7Benign:1
Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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MFSD8-related disorderBenign:1
Oct 24, 2023
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -