rs150219390

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022369.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	NM_022369.4	MANE Select	c.946G>A	p.Val316Met	missense	Exon 12 of 19	NP_071764.3
	STRA6	NM_001199042.2		c.1063G>A	p.Val355Met	missense	Exon 12 of 19	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.1057G>A	p.Val353Met	missense	Exon 12 of 19	NP_001185969.1	Q9BX79-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.946G>A	p.Val316Met	missense	Exon 12 of 19	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.1063G>A	p.Val355Met	missense	Exon 12 of 19	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.919G>A	p.Val307Met	missense	Exon 12 of 19	ENSP00000413012.2	Q9BX79-3

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

GnomAD2 exomes AF: 0.000755 AC: 169 AN: 223814 AF XY: 0.000680

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 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

African (AFR) AF: 0.0122 AC: 407 AN: 33324

American (AMR) AF: 0.000306 AC: 13 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: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106064

Other (OTH) AF: 0.000567 AC: 34 AN: 59930

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

African (AFR) AF: 0.0113 AC: 470 AN: 41576

American (AMR) AF: 0.00111 AC: 17 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00132 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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Matthew-Wood syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0085	T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.90
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.61
MVP		0.84
MPC		0.45
ClinPred		0.023	T
GERP RS		5.1
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.31
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150219390; hg19: chr15-74481600;