Variant rs869025269 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_022369.4(STRA6):c.1313A>G(p.Gln438Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,457,384 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: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

STRA6
NM_022369.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.38

Variant links:

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]

STRA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

PP5

Variant 15-74182448-T-C is Pathogenic according to our data. Variant chr15-74182448-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 221966.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRA6	NM_022369.4 link	c.1313A>G	p.Gln438Arg	missense_variant	15/19	ENST00000395105.9	NP_071764.3	Q9BX79-1B3KPB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9 link	c.1313A>G	p.Gln438Arg	missense_variant	15/19	1	NM_022369.4	ENSP00000378537.4		Q9BX79-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000833

AC:

AN:

240096

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

130078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1457384

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anophthalmia-microphthalmia syndrome

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

rare variant, predicted damaging in silico (Polyphen-2, SIFT), compound heterozygosity -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.;D;D;.;D;.;.;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T;.;.;T;T;T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.39

MutationAssessor

Uncertain

2.9

M;.;M;M;.;M;.;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.3

N;N;N;.;.;.;N;.;.

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

D;D;D;.;.;.;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D;.;D;.

Vest4

0.75

MutPred

0.87

Gain of solvent accessibility (P = 0.0584);.;Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);.;Gain of solvent accessibility (P = 0.0584);.;.;.;

MVP

0.85

MPC

0.46

ClinPred

0.95

GERP RS

4.9

Varity_R

0.65

gMVP

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over