Genetic Variant SPATA31A6:p.Gly37Val (chr9-42183797-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001145196.1(SPATA31A6):c.110G>T(p.Gly37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,534,886 control chromosomes in the GnomAD database, including 37 homozygotes. 9/15 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. G37R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000044 ( 1 hom., cov: 23)

Exomes 𝑓: 0.00012 ( 36 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.402

Publications

5 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 -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 36 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.110G>T	p.Gly37Val	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.110G>T	p.Gly37Val	missense	Exon 1 of 4	ENSP00000329825.6	Q5VVP1

Frequencies

GnomAD3 genomes

AF:

0.0000443

AC:

AN:

135470

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000241

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000624

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000121

AC:

170

AN:

1399316

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

116

AN XY:

696410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29250

American (AMR)

AF:

0.00

AC:

AN:

42816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24656

East Asian (EAS)

AF:

0.00

AC:

AN:

37236

South Asian (SAS)

AF:

0.00110

AC:

AN:

82554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47390

Middle Eastern (MID)

AF:

0.000252

AC:

AN:

3962

European-Non Finnish (NFE)

AF:

0.0000661

AC:

AN:

1073932

Other (OTH)

AF:

0.000122

AC:

AN:

57520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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:

0.0000443

AC:

AN:

135570

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

65984

show subpopulations

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

African (AFR)

AF:

0.0000301

AC:

AN:

33242

American (AMR)

AF:

0.00

AC:

AN:

13660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3204

East Asian (EAS)

AF:

0.00

AC:

AN:

4470

South Asian (SAS)

AF:

0.000241

AC:

AN:

4156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000624

AC:

AN:

64080

Other (OTH)

AF:

0.00

AC:

AN:

1872

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00194621), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.00

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

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.5

(source)

DEOGEN2

Benign

0.085

Eigen

Benign

-0.071

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.53

M_CAP

Benign

0.0038

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.1

PhyloP100

0.40

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.3

Sift

Benign

0.74

Sift4G

Uncertain

0.0060

Vest4

0.64

MutPred

0.38

Gain of catalytic residue at G37 (P = 0.096)

MVP

0.25

ClinPred

0.18

GERP RS

2.7

PromoterAI

0.011

Neutral

(source)

gMVP

0.14

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