Genetic Variant SPATA31A6:p.Gly115Cys (chr9-42186045-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145196.1(SPATA31A6):c.343G>T(p.Gly115Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 16)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.988

Variant links:

Genes affected

SPATA31A6 (HGNC:32006): (SPATA31 subfamily A member 6) Predicted to enable actin binding activity. Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08369088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1 link	c.343G>T	p.Gly115Cys	missense_variant	Exon 4 of 4	ENST00000332857.7	NP_001138668.1	Q5VVP1
SPATA31A6	XM_011517871.4 link	c.379G>T	p.Gly127Cys	missense_variant	Exon 4 of 4		XP_011516173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31A6	ENST00000332857.7 link	c.343G>T	p.Gly115Cys	missense_variant	Exon 4 of 4	1	NM_001145196.1	ENSP00000329825.6		Q5VVP1
SPATA31A6	ENST00000496386.1 link	n.194G>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

107206

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.61e-7

AC:

AN:

1314904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

647894

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27494

American (AMR)

AF:

0.00

AC:

AN:

30356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20442

East Asian (EAS)

AF:

0.00

AC:

AN:

35434

South Asian (SAS)

AF:

0.00

AC:

AN:

70854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3678

European-Non Finnish (NFE)

AF:

9.76e-7

AC:

AN:

1025072

Other (OTH)

AF:

0.00

AC:

AN:

54220

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

107206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

51670

African (AFR)

AF:

0.00

AC:

AN:

26296

American (AMR)

AF:

0.00

AC:

AN:

10382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2484

East Asian (EAS)

AF:

0.00

AC:

AN:

2920

South Asian (SAS)

AF:

0.00

AC:

AN:

3166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51716

Other (OTH)

AF:

0.00

AC:

AN:

1466

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.343G>T (p.G115C) alteration is located in exon 4 (coding exon 4) of the SPATA31A6 gene. This alteration results from a G to T substitution at nucleotide position 343, causing the glycine (G) at amino acid position 115 to be replaced by a cysteine (C). 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

0.098

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.61

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.50

M_CAP

Benign

0.0011

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.99

PhyloP100

-0.99

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

Sift

Benign

0.052

Sift4G

Benign

0.10

Vest4

0.15

MutPred

0.26

Loss of phosphorylation at S118 (P = 0.1077);

MVP

0.14

ClinPred

0.041

GERP RS

-2.2

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Loading publications...

chr9-42186045-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over