GeneBe

rs118203978

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_001371596.2(MFSD8):​c.362A>T​(p.Tyr121Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y121C) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

MFSD8
NM_001371596.2 missense

Scores

6
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.02
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr4-127943829-T-C is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MFSD8NM_001371596.2 linkc.362A>T p.Tyr121Phe missense_variant Exon 4 of 12 ENST00000641686.2 NP_001358525.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MFSD8ENST00000641686.2 linkc.362A>T p.Tyr121Phe missense_variant Exon 4 of 12 NM_001371596.2 ENSP00000493218.2 Q8NHS3-1

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
0.14
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;T;.;.;.;.;.;.;.;.;.;.;D;.;.;T;.;.;.;.;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
.;.;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.88
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Pathogenic
3.2
M;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.9
.;D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.
REVEL
Uncertain
0.57
Sift
Pathogenic
0.0
.;D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.
Sift4G
Pathogenic
0.0
.;D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.
Polyphen
1.0
D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.
Vest4
0.69, 0.69
MutPred
0.81
Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);.;.;.;Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);.;Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);.;Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);Gain of catalytic residue at H125 (P = 0.1327);.;Gain of catalytic residue at H125 (P = 0.1327);
MVP
0.66
MPC
0.48
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.74
gMVP
0.55

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: chr4-128864984; API