4-127943875-G-C

Position:

• chr4-127943875-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371596.2(MFSD8):​c.316C>G​(p.Pro106Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFSD8 NM_001371596.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99

Genes affected

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD8	NM_001371596.2	c.316C>G	p.Pro106Ala	missense_variant	4/12	ENST00000641686.2	NP_001358525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD8	ENST00000641686.2	c.316C>G	p.Pro106Ala	missense_variant	4/12		NM_001371596.2	ENSP00000493218.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.46	T;T;.;.;.;.;.;.;.;.;.;.;D;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	.;.;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.2	M;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.1	.;D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.32
Sift	Benign	0.057	.;T;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.
Sift4G	Pathogenic	0.0	.;D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.
Polyphen		1.0	D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;P;.;.;.;.;.
Vest4		0.51, 0.52
MutPred		0.70		Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);.;.;.;Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);.;Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);.;Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);Loss of glycosylation at P102 (P = 0.0249);.;Loss of glycosylation at P102 (P = 0.0249);
MVP		0.80
MPC		0.49
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-128865030;