Genetic Variant SPATA31D3:p.Gly727Asp (chr9-81947433-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207416.3(SPATA31D3):c.2180G>A(p.Gly727Asp) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G727V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000075 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D3
NM_207416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.708

Publications

0 publications found

Variant links:

Genes affected

SPATA31D3 (HGNC:38603): (SPATA31 subfamily D member 3) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31D3 links:

ENSG00000267559 (HGNC:):

ENSG00000267559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025347859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA31D3	NM_207416.3	MANE Select	c.2180G>A	p.Gly727Asp	missense	Exon 4 of 4	NP_997299.2	P0C874
LOC105376105	NR_188610.1		n.943-947C>T		intron	N/A
LOC105376105	NR_188611.1		n.943-947C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA31D3	ENST00000445385.3	TSL:1 MANE Select	c.2180G>A	p.Gly727Asp	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
ENSG00000267559	ENST00000585776.5	TSL:2	n.943-947C>T		intron	N/A
ENSG00000267559	ENST00000592744.1	TSL:4	n.519-947C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000736

AC:

AN:

81518

Hom.:

Cov.:

show subpopulations

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:

0.000146

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000566

AC:

AN:

106014

AF XY:

0.0000901

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:

0.000151

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000752

AC:

AN:

1116876

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

558704

show subpopulations

African (AFR)

AF:

0.0000404

AC:

AN:

24764

American (AMR)

AF:

0.00

AC:

AN:

31220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22248

East Asian (EAS)

AF:

0.00

AC:

AN:

33326

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69532

European-Finnish (FIN)

AF:

0.000127

AC:

AN:

47316

Middle Eastern (MID)

AF:

0.00113

AC:

AN:

4444

European-Non Finnish (NFE)

AF:

0.0000802

AC:

AN:

835748

Other (OTH)

AF:

0.0000829

AC:

AN:

48278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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: AS_VQSR

AF:

0.0000736

AC:

AN:

81518

Hom.:

Cov.:

AF XY:

0.0000526

AC XY:

AN XY:

38036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20478

American (AMR)

AF:

0.00

AC:

AN:

7184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2226

East Asian (EAS)

AF:

0.00

AC:

AN:

2124

South Asian (SAS)

AF:

0.00

AC:

AN:

1592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

182

European-Non Finnish (NFE)

AF:

0.000146

AC:

AN:

41192

Other (OTH)

AF:

0.00

AC:

AN:

964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000193

Hom.:

ExAC

AF:

0.0000685

AC:

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

0.25

BayesDel_noAF

Benign

-0.92

CADD

Benign

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.055

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.49

MetaRNN

Benign

0.025

MutationAssessor

Uncertain

2.5

PhyloP100

-0.71

PrimateAI

Benign

0.46

Sift4G

Benign

0.072

Polyphen

0.95

Vest4

0.083

GERP RS

0.26

Varity_R

0.071

gMVP

0.062

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