Genetic Variant SPATA31A7:p.Arg68Trp (chr9-61191465-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015667.2(SPATA31A7):c.202C>T(p.Arg68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,272,846 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 6 hom., cov: 17)

Exomes 𝑓: 0.00013 ( 46 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31A7
NM_015667.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.690

Variant links:

Genes affected

SPATA31A7 (HGNC:32007): (SPATA31 subfamily A member 7) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31A7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09756231).

BS2

High Homozygotes in GnomAdExome4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A7	NM_015667.2 link	c.202C>T	p.Arg68Trp	missense_variant	Exon 2 of 4	ENST00000619167.2	NP_056482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31A7	ENST00000619167.2 link	c.202C>T	p.Arg68Trp	missense_variant	Exon 2 of 4	1	NM_015667.2	ENSP00000484807.1		Q8IWB4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

116286

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000884

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:

0.000351

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000553

AC:

AN:

235194

Hom.:

AF XY:

0.0000391

AC XY:

AN XY:

127848

show subpopulations

Gnomad AFR exome

AF:

0.000886

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000486

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

166

AN:

1272846

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

101

AN XY:

631634

show subpopulations

Gnomad4 AFR exome

AF:

0.0000800

Gnomad4 AMR exome

AF:

0.0000528

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000310

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.0000969

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000181

AC:

AN:

116286

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

56234

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000884

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000351

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202C>T (p.R68W) alteration is located in exon 2 (coding exon 2) of the SPATA31A7 gene. This alteration results from a C to T substitution at nucleotide position 202, causing the arginine (R) at amino acid position 68 to be replaced by a tryptophan (W). 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_noAF

Benign

-0.98

CADD

Benign

9.1

DANN

Benign

0.72

DEOGEN2

Benign

0.027

LIST_S2

Benign

0.50

MetaRNN

Benign

0.098

Sift4G

Benign

0.094

Vest4

0.22

gMVP

0.20

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