Variant 7-135246541-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394401.1(STRA8):c.718G>A(p.Glu240Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,420,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

STRA8
NM_001394401.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

Variant links:

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]

STRA8 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STRA8	NM_001394401.1 linkuse as main transcript	c.718G>A	p.Glu240Lys	missense_variant	6/9	ENST00000662584.2
STRA8	NM_182489.3 linkuse as main transcript	c.505G>A	p.Glu169Lys	missense_variant	6/9
STRA8	XM_011516137.3 linkuse as main transcript	c.718G>A	p.Glu240Lys	missense_variant	5/8
STRA8	XM_047420324.1 linkuse as main transcript	c.718G>A	p.Glu240Lys	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
STRA8	ENST00000662584.2 linkuse as main transcript	c.718G>A	p.Glu240Lys	missense_variant	6/9		NM_001394401.1	P2
STRA8	ENST00000275764.3 linkuse as main transcript	c.571G>A	p.Glu191Lys	missense_variant	6/9	1		A2
	ENST00000637483.1 linkuse as main transcript	n.761C>T		non_coding_transcript_exon_variant	5/5	5
STRA8	ENST00000667288.1 linkuse as main transcript	c.505G>A	p.Glu169Lys	missense_variant	6/9			A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000556

AC:

AN:

179766

Hom.:

AF XY:

0.00

AC XY:

AN XY:

97036

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000358

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000211

AC:

AN:

1420732

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000845

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.571G>A (p.E191K) alteration is located in exon 6 (coding exon 6) of the STRA8 gene. This alteration results from a G to A substitution at nucleotide position 571, causing the glutamic acid (E) at amino acid position 191 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

M_CAP

Benign

0.0055

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.23

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.012

Polyphen

0.99

Vest4

0.54

MutPred

0.32

Gain of MoRF binding (P = 0.0051);

MVP

0.47

MPC

1.1

ClinPred

0.95

GERP RS

5.9

Varity_R

0.35

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over