Genetic Variant SPATA31D4:p.Gly803Glu (chr9-81932569-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001145197.1(SPATA31D4):c.2408G>A(p.Gly803Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000921 in 1,367,846 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 4 hom., cov: 20)

Exomes 𝑓: 0.000092 ( 17 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D4
NM_001145197.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

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:

ENSG00000267559 (HGNC:):

ENSG00000267559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073988736).

BP6

Variant 9-81932569-G-A is Benign according to our data. Variant chr9-81932569-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2297308.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 gene

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.2408G>A	p.Gly803Glu	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
LOC105376105	NR_188610.1		n.1040-1175C>T		intron	N/A
LOC105376105	NR_188611.1		n.1229-1175C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2408G>A	p.Gly803Glu	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-1175C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000577

AC:

AN:

133470

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000467

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:

0.000115

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000144

AC:

AN:

229866

AF XY:

0.0000718

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.0000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000921

AC:

126

AN:

1367846

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

681796

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

30986

American (AMR)

AF:

0.000119

AC:

AN:

41876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25158

East Asian (EAS)

AF:

0.00

AC:

AN:

39168

South Asian (SAS)

AF:

0.0000951

AC:

AN:

84166

European-Finnish (FIN)

AF:

0.0000200

AC:

AN:

49954

Middle Eastern (MID)

AF:

0.000552

AC:

AN:

5434

European-Non Finnish (NFE)

AF:

0.0000242

AC:

AN:

1034254

Other (OTH)

AF:

0.000246

AC:

AN:

56850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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: AS_VQSR

AF:

0.000584

AC:

AN:

133564

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

AN XY:

65032

show subpopulations

African (AFR)

AF:

0.00184

AC:

AN:

35310

American (AMR)

AF:

0.000466

AC:

AN:

12882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3226

East Asian (EAS)

AF:

0.00

AC:

AN:

4966

South Asian (SAS)

AF:

0.00

AC:

AN:

4468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000115

AC:

AN:

60870

Other (OTH)

AF:

0.00

AC:

AN:

1840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000438

Hom.:

ExAC

AF:

0.000221

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.057

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0070

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0011

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0074

MutationAssessor

Benign

-0.72

PhyloP100

-1.7

PrimateAI

Benign

0.42

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.015

GERP RS

0.67

Varity_R

0.14

gMVP

0.038

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over