Genetic Variant SPATA31D4:p.Arg695Cys (chr9-81932244-C-T) – 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_001145197.1(SPATA31D4):c.2083C>T(p.Arg695Cys) 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 0.00037 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00041 ( 22 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D4
NM_001145197.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.468

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007330984).

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.2083C>T	p.Arg695Cys	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
LOC105376105	NR_188610.1		n.1040-850G>A		intron	N/A
LOC105376105	NR_188611.1		n.1229-850G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2083C>T	p.Arg695Cys	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-850G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

40712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00839

Gnomad EAS

AF:

0.00199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000532

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000807

AC:

AN:

52058

AF XY:

0.000797

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00467

Gnomad EAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000413

AC:

229

AN:

555106

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

105

AN XY:

287380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14350

American (AMR)

AF:

0.00

AC:

AN:

20456

Ashkenazi Jewish (ASJ)

AF:

0.00661

AC:

AN:

14518

East Asian (EAS)

AF:

0.00256

AC:

AN:

31606

South Asian (SAS)

AF:

0.0000209

AC:

AN:

47932

European-Finnish (FIN)

AF:

0.0000339

AC:

AN:

29528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2112

European-Non Finnish (NFE)

AF:

0.0000821

AC:

AN:

365586

Other (OTH)

AF:

0.000689

AC:

AN:

29018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000368

AC:

AN:

40764

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

18594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10580

American (AMR)

AF:

0.00

AC:

AN:

3854

Ashkenazi Jewish (ASJ)

AF:

0.00839

AC:

AN:

1192

East Asian (EAS)

AF:

0.00200

AC:

AN:

2000

South Asian (SAS)

AF:

0.00

AC:

AN:

1078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.0000532

AC:

AN:

18806

Other (OTH)

AF:

0.00

AC:

AN:

554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000169

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

0.11

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0073

MutationAssessor

Benign

1.2

PhyloP100

0.47

PrimateAI

Uncertain

0.59

Sift4G

Uncertain

0.0020

Polyphen

0.0040

Vest4

0.21

GERP RS

0.67

Varity_R

0.17

gMVP

0.023

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

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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