rs118203961

chr15-74196145-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_022369.4(STRA6):c.269C>T(p.Pro90Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STRA6 NM_022369.4 missense, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.23

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984
• PP5: Variant 15-74196145-G-A is Pathogenic according to our data. Variant chr15-74196145-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1137.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74196145-G-A is described in UniProt as null. Variant chr15-74196145-G-A is described in UniProt as null. Variant chr15-74196145-G-A is described in UniProt as null. Variant chr15-74196145-G-A is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA6	NM_022369.4	c.269C>T	p.Pro90Leu	missense_variant, splice_region_variant	5/19	ENST00000395105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA6	ENST00000395105.9	c.269C>T	p.Pro90Leu	missense_variant, splice_region_variant	5/19	1	NM_022369.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Matthew-Wood syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;D;D;.;D;.;.;.;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.9	M;M;M;.;M;.;.;.;M
MutationTaster	Benign	1.0	A;A;A;A;A;A;A;A;A
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.5	D;D;.;.;.;D;.;.;D
REVEL	Pathogenic	0.93
Sift	Benign	0.054	T;T;.;.;.;D;.;.;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;.;D;.;D;.;D
Vest4		0.92
MutPred		0.92		Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);.;.;.;Loss of disorder (P = 0.0204);
MVP		0.94
MPC		0.45
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs118203961; hg19: chr15-74488486;