2-190436304-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_017694.4(MFSD6):c.275A>G(p.Tyr92Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MFSD6
NM_017694.4 missense
NM_017694.4 missense
Scores
14
2
1
Clinical Significance
Conservation
PhyloP100: 9.11
Genes affected
MFSD6 (HGNC:24711): (major facilitator superfamily domain containing 6) Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, MFSD6
PP3
MetaRNN computational evidence supports a deleterious effect, 0.916
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFSD6 | NM_017694.4 | c.275A>G | p.Tyr92Cys | missense_variant | 3/8 | ENST00000392328.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFSD6 | ENST00000392328.6 | c.275A>G | p.Tyr92Cys | missense_variant | 3/8 | 2 | NM_017694.4 | P1 | |
MFSD6 | ENST00000281416.11 | c.275A>G | p.Tyr92Cys | missense_variant | 1/6 | 1 | P1 | ||
MFSD6 | ENST00000445546.1 | c.275A>G | p.Tyr92Cys | missense_variant | 2/2 | 4 | |||
MFSD6 | ENST00000432036.5 | c.275A>G | p.Tyr92Cys | missense_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.275A>G (p.Y92C) alteration is located in exon 3 (coding exon 1) of the MFSD6 gene. This alteration results from a A to G substitution at nucleotide position 275, causing the tyrosine (Y) at amino acid position 92 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;D;.;D
Vest4
0.92, 0.92
MutPred
Loss of ubiquitination at K94 (P = 0.0609);Loss of ubiquitination at K94 (P = 0.0609);Loss of ubiquitination at K94 (P = 0.0609);Loss of ubiquitination at K94 (P = 0.0609);
MVP
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at