Genetic Variant SPATA31A6:p.Gly115Arg (chr9-42186045-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145196.1(SPATA31A6):c.343G>C(p.Gly115Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G115C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0000046 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0404768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1 link	c.343G>C	p.Gly115Arg	missense_variant	Exon 4 of 4	ENST00000332857.7	NP_001138668.1	Q5VVP1
SPATA31A6	XM_011517871.4 link	c.379G>C	p.Gly127Arg	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>C	p.Gly115Arg	missense_variant	Exon 4 of 4	1	NM_001145196.1	ENSP00000329825.6		Q5VVP1
SPATA31A6	ENST00000496386.1 link	n.194G>C		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00000933

AC:

AN:

107208

Hom.:

Cov.:

show subpopulations

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:

0.0000193

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000456

AC:

AN:

1314904

Hom.:

Cov.:

AF XY:

0.00000926

AC XY:

AN XY:

647894

show subpopulations

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:

0.00000585

AC:

AN:

1025072

Other (OTH)

AF:

0.00

AC:

AN:

54220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000933

AC:

AN:

107208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

51670

show subpopulations

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

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:

0.0000193

AC:

AN:

51718

Other (OTH)

AF:

0.00

AC:

AN:

1466

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.21

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.00021

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00034

LIST_S2

Benign

0.60

M_CAP

Benign

0.00083

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.94

PhyloP100

-0.99

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.37

Sift

Benign

0.13

Sift4G

Benign

0.18

Vest4

0.089

MutPred

0.27

Gain of solvent accessibility (P = 0.0128);

MVP

0.055

ClinPred

0.11

GERP RS

-2.2

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over