Genetic Variant SPATA31D4:p.Asp791Glu (chr9-81932534-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001145197.1(SPATA31D4):c.2373C>G(p.Asp791Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0025 ( 1658 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D4
NM_001145197.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.29

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034041107).

BP6

Variant 9-81932534-C-G is Benign according to our data. Variant chr9-81932534-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2408203.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2373C>G	p.Asp791Glu	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
LOC105376105	NR_188610.1		n.1040-1140G>C		intron	N/A
LOC105376105	NR_188611.1		n.1229-1140G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2373C>G	p.Asp791Glu	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-1140G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000303

AC:

AN:

128582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000754

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000323

Gnomad ASJ

AF:

0.000319

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000227

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000136

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00532

AC:

1220

AN:

229388

AF XY:

0.00480

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.00983

Gnomad ASJ exome

AF:

0.000943

Gnomad EAS exome

AF:

0.00113

Gnomad FIN exome

AF:

0.000820

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00253

AC:

3415

AN:

1350318

Hom.:

1658

Cov.:

AF XY:

0.00256

AC XY:

1726

AN XY:

673012

show subpopulations

African (AFR)

AF:

0.0155

AC:

464

AN:

29926

American (AMR)

AF:

0.00886

AC:

352

AN:

39742

Ashkenazi Jewish (ASJ)

AF:

0.00222

AC:

AN:

24736

East Asian (EAS)

AF:

0.000410

AC:

AN:

39024

South Asian (SAS)

AF:

0.00191

AC:

159

AN:

83430

European-Finnish (FIN)

AF:

0.00335

AC:

163

AN:

48656

Middle Eastern (MID)

AF:

0.00185

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00200

AC:

2045

AN:

1023532

Other (OTH)

AF:

0.00270

AC:

151

AN:

55878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

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

100

<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:

0.000303

AC:

AN:

128672

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

62770

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000753

AC:

AN:

33220

American (AMR)

AF:

0.000323

AC:

AN:

12388

Ashkenazi Jewish (ASJ)

AF:

0.000319

AC:

AN:

3138

East Asian (EAS)

AF:

0.00

AC:

AN:

4902

South Asian (SAS)

AF:

0.000227

AC:

AN:

4402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000136

AC:

AN:

59020

Other (OTH)

AF:

0.00

AC:

AN:

1754

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.242

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:

0.00880

Hom.:

ExAC

AF:

0.0000177

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

0.11

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0020

(source)

DANN

Benign

0.24

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0034

PhyloP100

-6.3

PrimateAI

Benign

0.37

Sift4G

Benign

0.36

Vest4

0.027

GERP RS

-1.7

Varity_R

0.037

gMVP

0.030

Mutation Taster

=100/0

polymorphism (auto)

(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

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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