15-74202231-CG-CGGG

Variant names:

• chr15-74202231-C-CGG
• rs1555457919
• NM_022369.4:c.35_36dupCC

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_022369.4(STRA6):​c.35_36dupCC​(p.Gly13ProfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,384,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P12P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: STRA6 NM_022369.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -2.25
• 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: Likely_pathogenic. The variant received 9 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 27 pathogenic variants in the truncated region.
• PP5: Variant 15-74202231-C-CGG is Pathogenic according to our data. Variant chr15-74202231-C-CGG is described in ClinVar as Pathogenic. ClinVar VariationId is 1141.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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	NM_022369.4	MANE Select	c.35_36dupCC	p.Gly13ProfsTer60	frameshift	Exon 2 of 19	NP_071764.3
	STRA6	NM_001199042.2		c.152_153dupCC	p.Gly52ProfsTer60	frameshift	Exon 2 of 19	NP_001185971.1
	STRA6	NM_001199040.2		c.146_147dupCC	p.Gly50ProfsTer60	frameshift	Exon 2 of 19	NP_001185969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.35_36dupCC	p.Gly13ProfsTer60	frameshift	Exon 2 of 19	ENSP00000378537.4
	STRA6	ENST00000563965.5	TSL:1	c.152_153dupCC	p.Gly52ProfsTer60	frameshift	Exon 2 of 19	ENSP00000456609.1
	STRA6	ENST00000423167.6	TSL:1	c.35_36dupCC	p.Gly13ProfsTer60	frameshift	Exon 2 of 19	ENSP00000413012.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 188044 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000867 AC: 12 AN: 1384830 Hom.: 0 Cov.: 32 AF XY: 0.00000733 AC XY: 5 AN XY: 682262

African (AFR) AF: 0.00 AC: 0 AN: 30532

American (AMR) AF: 0.00 AC: 0 AN: 30864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39132

South Asian (SAS) AF: 0.00 AC: 0 AN: 70714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5386

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1079736

Other (OTH) AF: 0.00 AC: 0 AN: 57046

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Matthew-Wood syndrome Pathogenic:1

Mar 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1555457919; hg19: chr15-74494572;