15-74194695-T-G

Variant names:

• chr15-74194695-T-G
• rs351224
• ENST00000432245.6:c.*907A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000432245.6(STRA6):​c.*907A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRA6 ENST00000432245.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 13 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432245.6. 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.597+607A>C		intron	N/A	NP_071764.3
	STRA6	NM_001142620.2		c.*907A>C		3_prime_UTR	Exon 6 of 6	NP_001136092.1
	STRA6	NM_001199042.2		c.714+607A>C		intron	N/A	NP_001185971.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRA6	ENST00000432245.6	TSL:1	c.*907A>C		3_prime_UTR	Exon 6 of 6	ENSP00000407176.2
	STRA6	ENST00000395105.9	TSL:1 MANE Select	c.597+607A>C		intron	N/A	ENSP00000378537.4
	STRA6	ENST00000563965.5	TSL:1	c.714+607A>C		intron	N/A	ENSP00000456609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 939912 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 448706

African (AFR) AF: 0.00 AC: 0 AN: 20058

American (AMR) AF: 0.00 AC: 0 AN: 11108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13642

East Asian (EAS) AF: 0.00 AC: 0 AN: 26732

South Asian (SAS) AF: 0.00 AC: 0 AN: 17396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 787486

Other (OTH) AF: 0.00 AC: 0 AN: 39492

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.82
PhyloP100		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs351224; hg19: chr15-74487036;