7-135245459-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001394401.1(STRA8):c.525G>A(p.Glu175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 716,406 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: STRA8 NM_001394401.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.629

Genes affected

STRA8 (HGNC:30653): (stimulated by retinoic acid 8) This gene encodes a retinoic acid-responsive protein. A homologous protein in mouse has been shown to be involved in the regulation of meiotic initiation in both spermatogenesis and oogenesis, though feature differences between the mouse and human proteins suggest that these homologs are not entirely functionally equivalent. It is thought that this gene may play a role in spermatogenesis in humans. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-135245459-G-A is Benign according to our data. Variant chr7-135245459-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.629 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA8	NM_001394401.1	c.525G>A	p.Glu175=	synonymous_variant	5/9	ENST00000662584.2
STRA8	XM_011516137.3	c.525G>A	p.Glu175=	synonymous_variant	4/8
STRA8	XM_047420324.1	c.525G>A	p.Glu175=	synonymous_variant	5/9
STRA8	NM_182489.3	c.380+130G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA8	ENST00000662584.2	c.525G>A	p.Glu175=	synonymous_variant	5/9		NM_001394401.1	P2
STRA8	ENST00000275764.3	c.446+130G>A		intron_variant		1		A2
STRA8	ENST00000667288.1	c.380+130G>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.000671 AC: 102 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000548 AC: 309 AN: 564244 Hom.: 1 AF XY: 0.000527 AC XY: 162 AN XY: 307124

Gnomad4 AFR exome AF: 0.00128

Gnomad4 AMR exome AF: 0.000684

Gnomad4 ASJ exome AF: 0.00643

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000479

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000313

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.000670 AC: 102 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74382

Gnomad4 AFR AF: 0.000988

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000693 Hom.: 0

Bravo AF: 0.000827

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

STRA8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.26
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs189150814; hg19: chr7-134930211;