rs606231126

Variant names:

• chr15-74202216-AGT-GG
• rs606231126
• NM_022369.4:c.50_52delACTinsCC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_022369.4(STRA6):​c.50_52delACTinsCC​(p.Asp17AlafsTer55) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STRA6 NM_022369.4 frameshift, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.56
• Publications: 1 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-74202216-AGT-GG is Pathogenic according to our data. Variant chr15-74202216-AGT-GG is described in ClinVar as Pathogenic. ClinVar VariationId is 1139.Status of the report is no_assertion_criteria_provided, 0 stars.

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.50_52delACTinsCC	p.Asp17AlafsTer55	frameshift missense	Exon 2 of 19	NP_071764.3
	STRA6	NM_001199042.2		c.167_169delACTinsCC	p.Asp56AlafsTer55	frameshift missense	Exon 2 of 19	NP_001185971.1	Q9BX79-4
	STRA6	NM_001199040.2		c.161_163delACTinsCC	p.Asp54AlafsTer55	frameshift missense	Exon 2 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.50_52delACTinsCC	p.Asp17AlafsTer55	frameshift missense	Exon 2 of 19	ENSP00000378537.4	Q9BX79-1
	STRA6	ENST00000563965.5	TSL:1	c.167_169delACTinsCC	p.Asp56AlafsTer55	frameshift missense	Exon 2 of 19	ENSP00000456609.1	Q9BX79-4
	STRA6	ENST00000423167.6	TSL:1	c.50_52delACTinsCC	p.Asp17AlafsTer55	frameshift missense	Exon 2 of 19	ENSP00000413012.2	Q9BX79-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs606231126; hg19: chr15-74494557;