Genetic Variant SPATA31D4:p.Glu88Lys (chr9-81930129-G-A) – 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_001145197.1(SPATA31D4):c.262G>A(p.Glu88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 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: 0)

Exomes 𝑓: 0.000013 ( 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: 0.538

Publications

0 publications found

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:

ENSG00000230846 (HGNC:):

ENSG00000230846 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=0.11119923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145197.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA31D4	NM_001145197.1	MANE Select	c.262G>A	p.Glu88Lys	missense	Exon 3 of 4	NP_001138669.1	Q6ZUB0
LOC105376105	NR_188610.1		n.1325+980C>T		intron	N/A
LOC105376105	NR_188611.1		n.1514+980C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.262G>A	p.Glu88Lys	missense	Exon 3 of 4	ENSP00000488251.1	Q6ZUB0
ENSG00000230846	ENST00000427387.1	TSL:3	n.260+980C>T		intron	N/A
ENSG00000267559	ENST00000585776.5	TSL:2	n.*97C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

9798

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

GnomAD2 exomes

AF:

0.0000540

AC:

AN:

18522

AF XY:

0.000105

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000129

AC:

AN:

233188

Hom.:

Cov.:

AF XY:

0.00000800

AC XY:

AN XY:

125004

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:

5470

American (AMR)

AF:

0.00

AC:

AN:

5178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5986

East Asian (EAS)

AF:

0.00

AC:

AN:

2798

South Asian (SAS)

AF:

0.00

AC:

AN:

25484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

948

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

166076

Other (OTH)

AF:

0.00

AC:

AN:

10942

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

9798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4706

African (AFR)

AF:

0.00

AC:

AN:

2392

American (AMR)

AF:

0.00

AC:

AN:

620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

414

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5730

Other (OTH)

AF:

0.00

AC:

AN:

102

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.92

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.038

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.65

MetaRNN

Benign

0.11

MutationAssessor

Benign

1.8

PhyloP100

0.54

PrimateAI

Uncertain

0.51

Sift4G

Benign

0.14

Polyphen

0.67

Vest4

0.21

GERP RS

0.66

Varity_R

0.17

gMVP

0.060

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over