Genetic Variant SPATA6:p.Val257Met (chr1-48399362-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019073.4(SPATA6):c.769G>A(p.Val257Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATA6
NM_019073.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

SPATA6 (HGNC:18309): (spermatogenesis associated 6) Predicted to enable myosin light chain binding activity. Predicted to be involved in motile cilium assembly and spermatogenesis. Predicted to be located in extracellular region. Predicted to be active in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

SPATA6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3383819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA6	NM_019073.4 link	c.769G>A	p.Val257Met	missense_variant	Exon 7 of 13	ENST00000371847.8	NP_061946.1	Q9NWH7-1A0A140VJV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA6	ENST00000371847.8 link	c.769G>A	p.Val257Met	missense_variant	Exon 7 of 13	1	NM_019073.4	ENSP00000360913.3		Q9NWH7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249858

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.00000137

AC:

AN:

1460240

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.769G>A (p.V257M) alteration is located in exon 7 (coding exon 7) of the SPATA6 gene. This alteration results from a G to A substitution at nucleotide position 769, causing the valine (V) at amino acid position 257 to be replaced by a methionine (M). 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

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.1

L;.;L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.9

N;.;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;.;D;D

Sift4G

Uncertain

0.0030

D;D;D;.

Polyphen

1.0

D;.;D;.

Vest4

0.59

MutPred

0.32

Gain of ubiquitination at K253 (P = 0.0628);.;Gain of ubiquitination at K253 (P = 0.0628);.;

MVP

0.27

MPC

0.34

ClinPred

0.75

GERP RS

5.8

Varity_R

0.18

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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