rs150219390

Variant names:

• chr15-74189259-C-G
• rs150219390
• NM_022369.4:c.946G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-74189259-C-G
• chr15-74189259-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022369.4(STRA6):​c.946G>C​(p.Val316Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V316M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STRA6 NM_022369.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.901
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Matthew-Wood syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRA6	NM_022369.4	c.946G>C	p.Val316Leu	missense_variant	Exon 12 of 19	ENST00000395105.9	NP_071764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRA6	ENST00000395105.9	c.946G>C	p.Val316Leu	missense_variant	Exon 12 of 19	1	NM_022369.4	ENSP00000378537.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448882 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 719340

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33324

American (AMR) AF: 0.00 AC: 0 AN: 42450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 39278

South Asian (SAS) AF: 0.00 AC: 0 AN: 84000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106064

Other (OTH) AF: 0.00 AC: 0 AN: 59930

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;T;T;.;T;.;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	.;T;.;.;T;T;T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.6	M;.;M;M;.;M;.;.;.
PhyloP100		0.90
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N;N;N;N;.;.;N;N;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.012	D;D;D;T;.;.;D;D;.
Sift4G	Uncertain	0.029	D;D;D;D;D;D;D;D;D
Polyphen		0.97	D;D;D;D;.;D;.;D;.
Vest4		0.31
MutPred		0.56		Loss of catalytic residue at V316 (P = 0.0809);.;Loss of catalytic residue at V316 (P = 0.0809);Loss of catalytic residue at V316 (P = 0.0809);.;Loss of catalytic residue at V316 (P = 0.0809);.;.;.;
MVP		0.82
MPC		0.11
ClinPred		0.90	D
GERP RS		5.1
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.36
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150219390; hg19: chr15-74481600;