Genetic Variant SPATA31A6:p.Ser21Phe (chr9-42183749-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.62C>T(p.Ser21Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,535,814 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 10 hom., cov: 23)

Exomes 𝑓: 0.00062 ( 122 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.778

Publications

1 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=0.08620542).

BS2

High Homozygotes in GnomAd4 at 10 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.62C>T	p.Ser21Phe	missense	Exon 1 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.62C>T	p.Ser21Phe	missense	Exon 1 of 4	ENSP00000329825.6	Q5VVP1

Frequencies

GnomAD3 genomes

AF:

0.000543

AC:

AN:

134458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000741

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000924

Gnomad OTH

AF:

0.00108

GnomAD2 exomes

AF:

0.000514

AC:

120

AN:

233284

AF XY:

0.000550

show subpopulations

Gnomad AFR exome

AF:

0.000299

Gnomad AMR exome

AF:

0.000759

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000110

Gnomad NFE exome

AF:

0.000778

Gnomad OTH exome

AF:

0.000867

GnomAD4 exome

AF:

0.000624

AC:

875

AN:

1401252

Hom.:

122

Cov.:

AF XY:

0.000627

AC XY:

437

AN XY:

697396

show subpopulations

African (AFR)

AF:

0.000136

AC:

AN:

29318

American (AMR)

AF:

0.000841

AC:

AN:

42818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24678

East Asian (EAS)

AF:

0.00

AC:

AN:

37270

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83280

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

48324

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

3980

European-Non Finnish (NFE)

AF:

0.000738

AC:

793

AN:

1073960

Other (OTH)

AF:

0.000469

AC:

AN:

57624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

119

159

199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000543

AC:

AN:

134562

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

65442

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32810

American (AMR)

AF:

0.000740

AC:

AN:

13516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3200

East Asian (EAS)

AF:

0.00

AC:

AN:

4440

South Asian (SAS)

AF:

0.00

AC:

AN:

4094

European-Finnish (FIN)

AF:

0.000104

AC:

AN:

9650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000924

AC:

AN:

63826

Other (OTH)

AF:

0.00107

AC:

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.000488

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

0.12

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.0

(source)

DANN

Benign

0.096

DEOGEN2

Benign

0.00017

LIST_S2

Benign

0.41

MetaRNN

Benign

0.086

PhyloP100

-0.78

PROVEAN

Benign

-0.20

Sift

Benign

0.85

Sift4G

Benign

0.079

Vest4

0.52

PromoterAI

0.0076

Neutral

(source)

gMVP

0.090

Splicing

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