Genetic Variant SPATA31D4:p.His830Tyr (chr9-81932649-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001145197.1(SPATA31D4):c.2488C>T(p.His830Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000072 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D4
NM_001145197.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.250

Variant links:

Genes affected

SPATA31D4 (HGNC:38601): (SPATA31 subfamily D member 4) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31D4 links:

ENSG00000267559 (HGNC:):

ENSG00000267559 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40174422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D4	NM_001145197.1 link	c.2488C>T	p.His830Tyr	missense_variant	Exon 4 of 4	ENST00000419782.5	NP_001138669.1	Q6ZUB0
LOC105376105	NR_188610.1 link	n.1040-1255G>A		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1 link	n.1229-1255G>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D4	ENST00000419782.5 link	c.2488C>T	p.His830Tyr	missense_variant	Exon 4 of 4	1	NM_001145197.1	ENSP00000488251.1		Q6ZUB0
ENSG00000267559	ENST00000585776.5 link	n.1040-1255G>A		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

133180

Hom.:

Cov.:

FAILED QC

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:

0.000231

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000166

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183520

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

98488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000400

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000720

AC:

AN:

1389428

Hom.:

Cov.:

AF XY:

0.00000868

AC XY:

AN XY:

691056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000759

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000150

AC:

AN:

133180

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

64604

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000231

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000166

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000882

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2488C>T (p.H830Y) alteration is located in exon 4 (coding exon 4) of the SPATA31D4 gene. This alteration results from a C to T substitution at nucleotide position 2488, causing the histidine (H) at amino acid position 830 to be replaced by a tyrosine (Y). 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

0.32

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.70

MetaRNN

Benign

0.40

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.61

Sift4G

Uncertain

0.0050

Polyphen

0.88

Vest4

0.45

GERP RS

0.84

Varity_R

0.052

gMVP

0.16

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