7-135240670-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394401.1(STRA8):c.146A>G(p.Asn49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STRA8 NM_001394401.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.28

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04308617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRA8	NM_001394401.1	c.146A>G	p.Asn49Ser	missense_variant	2/9	ENST00000662584.2
STRA8	NM_182489.3	c.146A>G	p.Asn49Ser	missense_variant	2/9
STRA8	XM_011516137.3	c.146A>G	p.Asn49Ser	missense_variant	1/8
STRA8	XM_047420324.1	c.146A>G	p.Asn49Ser	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRA8	ENST00000662584.2	c.146A>G	p.Asn49Ser	missense_variant	2/9		NM_001394401.1	P2
STRA8	ENST00000275764.3	c.212A>G	p.Asn71Ser	missense_variant	2/9	1		A2
STRA8	ENST00000667288.1	c.146A>G	p.Asn49Ser	missense_variant	2/9			A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.212A>G (p.N71S) alteration is located in exon 2 (coding exon 2) of the STRA8 gene. This alteration results from a A to G substitution at nucleotide position 212, causing the asparagine (N) at amino acid position 71 to be replaced by a serine (S). 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	0.069
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	0.0020
Dann	Benign	0.54
DEOGEN2	Benign	0.27	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.043	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.16
Sift	Benign	0.32	T
Sift4G	Benign	0.65	T
Polyphen		0.0070	B
Vest4		0.092
MutPred		0.19		Gain of loop (P = 0.1069);
MVP		0.43
MPC		0.26
ClinPred		0.22	T
GERP RS		-0.36
Varity_R		0.043
gMVP		0.046

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: rs1832450231; hg19: chr7-134925422;