7-135240519-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000275764.3(STRA8):c.61C>T(p.Leu21Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

STRA8
ENST00000275764.3 missense, splice_region

Scores

Splicing: ADA: 0.001967

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.368

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0413993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
STRA8	NM_001394401.1 linkuse as main transcript	c.-6C>T	splice_region_variant, 5_prime_UTR_variant	2/9	ENST00000662584.2
STRA8	NM_182489.3 linkuse as main transcript	c.-6C>T	splice_region_variant, 5_prime_UTR_variant	2/9
STRA8	XM_011516137.3 linkuse as main transcript	c.-6C>T	5_prime_UTR_variant	1/8
STRA8	XM_047420324.1 linkuse as main transcript	c.-6C>T	splice_region_variant, 5_prime_UTR_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
STRA8	ENST00000275764.3 linkuse as main transcript	c.61C>T	p.Leu21Phe	missense_variant, splice_region_variant	2/9	1		A2
STRA8	ENST00000662584.2 linkuse as main transcript	c.-6C>T		splice_region_variant, 5_prime_UTR_variant	2/9		NM_001394401.1	P2
STRA8	ENST00000667288.1 linkuse as main transcript	c.-6C>T		splice_region_variant, 5_prime_UTR_variant	2/9			A2

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250456

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0000289

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:

0.00000547

AC:

AN:

1461448

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000165

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

May 04, 2023

The c.61C>T (p.L21F) alteration is located in exon 2 (coding exon 2) of the STRA8 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the leucine (L) at amino acid position 21 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

Cadd

Benign

4.9

Dann

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.41

M_CAP

Benign

0.0054

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.99

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.74

REVEL

Benign

0.011

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.027

Polyphen

0.043

Vest4

0.059

MVP

0.055

MPC

0.36

ClinPred

0.11

GERP RS

2.6

Varity_R

0.17

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0020

dbscSNV1_RF

Benign

0.22

SpliceAI score (max)

0.14

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