rs118203960
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_022369.4(STRA6):c.1931C>T(p.Thr644Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
STRA6
NM_022369.4 missense
NM_022369.4 missense
Scores
13
3
2
Clinical Significance
Conservation
PhyloP100: 6.13
Genes affected
STRA6 (HGNC:30650): (signaling receptor and transporter of retinol STRA6) The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Dec 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;
PP3
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MetaRNN computational evidence supports a deleterious effect, 0.914
PP5
?
Variant 15-74180153-G-A is Pathogenic according to our data. Variant chr15-74180153-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1136.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-74180153-G-A is described in UniProt as null. Variant chr15-74180153-G-A is described in UniProt as null. Variant chr15-74180153-G-A is described in UniProt as null. Variant chr15-74180153-G-A is described in UniProt as null. Variant chr15-74180153-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRA6 | NM_022369.4 | c.1931C>T | p.Thr644Met | missense_variant | 19/19 | ENST00000395105.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRA6 | ENST00000395105.9 | c.1931C>T | p.Thr644Met | missense_variant | 19/19 | 1 | NM_022369.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251074Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135734
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461658Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727142
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74370
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Matthew-Wood syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 644 of the STRA6 protein (p.Thr644Met). This variant is present in population databases (rs118203960, gnomAD 0.004%). This missense change has been observed in individual(s) with STRA6-related conditions (PMID: 17273977, 22283518, 25044680). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1136). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;D;D;.;D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;M;M;.;M;.;.;.
MutationTaster
Benign
A;A;A;A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;.;.;.;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;.;.;.;D;.;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;.;D;.;D;.
Vest4
MVP
MPC
0.50
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at