Genetic Variant SPATA31A6:p.Pro65Leu (chr9-42185073-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001145196.1(SPATA31A6):c.194C>T(p.Pro65Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,538,904 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 2 hom., cov: 24)

Exomes 𝑓: 0.000021 ( 5 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.501

Publications

0 publications found

Variant links:

Genes affected

SPATA31A6 (HGNC:32006): (SPATA31 subfamily A member 6) Predicted to enable actin binding activity. Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31A6 links:

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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=0.10119322).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145196.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31A6	NM_001145196.1	MANE Select	c.194C>T	p.Pro65Leu	missense	Exon 2 of 4	NP_001138668.1	Q5VVP1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31A6	ENST00000332857.7	TSL:1 MANE Select	c.194C>T	p.Pro65Leu	missense	Exon 2 of 4	ENSP00000329825.6	Q5VVP1
	SPATA31A6	ENST00000496386.1	TSL:5	n.-199C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

137188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000433

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:

0.0000621

Gnomad OTH

AF:

0.00372

GnomAD4 exome

AF:

0.0000207

AC:

AN:

1401716

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

697176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29308

American (AMR)

AF:

0.000210

AC:

AN:

42958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24590

East Asian (EAS)

AF:

0.00

AC:

AN:

36544

South Asian (SAS)

AF:

0.00

AC:

AN:

81836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5200

European-Non Finnish (NFE)

AF:

0.0000121

AC:

AN:

1072402

Other (OTH)

AF:

0.000122

AC:

AN:

57556

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

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

AF:

0.000153

AC:

AN:

137188

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

66818

show subpopulations

African (AFR)

AF:

0.000118

AC:

AN:

34008

American (AMR)

AF:

0.000433

AC:

AN:

13870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3236

East Asian (EAS)

AF:

0.00

AC:

AN:

4558

South Asian (SAS)

AF:

0.00

AC:

AN:

4158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000621

AC:

AN:

64408

Other (OTH)

AF:

0.00372

AC:

AN:

1882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

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:

0.00

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

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.22

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0016

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.56

M_CAP

Benign

0.0019

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.93

PhyloP100

-0.50

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.42

Sift

Benign

0.037

Sift4G

Uncertain

0.038

Vest4

0.17

MutPred

0.33

Gain of catalytic residue at P65 (P = 0.0371)

MVP

0.31

ClinPred

0.21

GERP RS

-0.91

gMVP

0.057

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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