rs150219390

chr15-74189259-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_022369.4(STRA6):c.946G>A(p.Val316Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000591 in 1,601,216 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (4 hom.)
• Consequence: STRA6 NM_022369.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.901

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008462548).
• BP6: Variant 15-74189259-C-T is Benign according to our data. Variant chr15-74189259-C-T is described in ClinVar as [Benign]. Clinvar id is 464036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00322 (490/152334) while in subpopulation AFR AF= 0.0113 (470/41576). AF 95% confidence interval is 0.0105. There are 1 homozygotes in gnomad4. There are 261 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_022369.4	c.946G>A	p.Val316Met	missense_variant	12/19	ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9	c.946G>A	p.Val316Met	missense_variant	12/19	1	NM_022369.4	P1

Frequencies

GnomAD3 genomes AF: 0.00322 AC: 490 AN: 152216 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000755 AC: 169 AN: 223814 Hom.: 1 AF XY: 0.000680 AC XY: 82 AN XY: 120642

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000361

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.000315 AC: 457 AN: 1448882 Hom.: 4 Cov.: 32 AF XY: 0.000268 AC XY: 193 AN XY: 719340

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.000306

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: 0.00000181

Gnomad4 OTH exome AF: 0.000567

GnomAD4 genome AF: 0.00322 AC: 490 AN: 152334 Hom.: 1 Cov.: 33 AF XY: 0.00350 AC XY: 261 AN XY: 74484

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000649 Hom.: 2

Bravo AF: 0.00363

ESP6500AA AF: 0.00957 AC: 42

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000891 AC: 108

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Matthew-Wood syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;T;T;.;T;.;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.87	D
MetaRNN	Benign	0.0085	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.6	M;.;M;M;.;M;.;.;.
MutationTaster	Benign	0.68	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N;N;N;.;.;N;N;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.0040	D;D;D;T;.;.;D;D;.
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;D;.;D;.
Vest4		0.61
MVP		0.84
MPC		0.45
ClinPred		0.023	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

Other links and lift over

dbSNP: rs150219390; hg19: chr15-74481600;