Variant 1-48395344-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019073.4(SPATA6):c.791C>A(p.Pro264Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000386 in 1,554,708 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPATA6
NM_019073.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2624847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA6	NM_019073.4 linkuse as main transcript	c.791C>A	p.Pro264Gln	missense_variant	8/13	ENST00000371847.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA6	ENST00000371847.8 linkuse as main transcript	c.791C>A	p.Pro264Gln	missense_variant	8/13	1	NM_019073.4	P4	Q9NWH7-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.000479

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1402922

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

697290

show subpopulations

Gnomad4 AFR exome

AF:

0.0000326

Gnomad4 AMR exome

AF:

0.00

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:

0.0000347

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151786

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.791C>A (p.P264Q) alteration is located in exon 8 (coding exon 8) of the SPATA6 gene. This alteration results from a C to A substitution at nucleotide position 791, causing the proline (P) at amino acid position 264 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0068

T;T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.1

L;.;L;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

N;.;N;D

REVEL

Benign

0.095

Sift

Benign

0.036

D;.;D;D

Sift4G

Benign

0.14

T;D;T;.

Polyphen

1.0

D;.;D;.

Vest4

0.63

MutPred

0.20

Loss of catalytic residue at P263 (P = 0.0117);.;Loss of catalytic residue at P263 (P = 0.0117);.;

MVP

0.40

MPC

0.34

ClinPred

0.93

GERP RS

4.7

Varity_R

0.15

gMVP

0.28

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