Genetic Variant NM_001145196.1:c.208C>T (chr9-42185087-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.208C>T(p.Arg70Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,540,684 control chromosomes in the GnomAD database, including 5 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000033 ( 5 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.14

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=0.07229307).

BS2

High Homozygotes in GnomAdExome4 at 5 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.208C>T	p.Arg70Trp	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.208C>T	p.Arg70Trp	missense	Exon 2 of 4	ENSP00000329825.6	Q5VVP1
	SPATA31A6	ENST00000496386.1	TSL:5	n.-185C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000726

AC:

AN:

137668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000717

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1403016

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

697926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29364

American (AMR)

AF:

0.000163

AC:

AN:

43032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24632

East Asian (EAS)

AF:

0.00

AC:

AN:

36746

South Asian (SAS)

AF:

0.0000487

AC:

AN:

82146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51368

Middle Eastern (MID)

AF:

0.000195

AC:

AN:

5124

European-Non Finnish (NFE)

AF:

0.0000308

AC:

AN:

1072992

Other (OTH)

AF:

0.0000347

AC:

AN:

57612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

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:

0.00000726

AC:

AN:

137668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34176

American (AMR)

AF:

0.0000717

AC:

AN:

13950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3240

East Asian (EAS)

AF:

0.00

AC:

AN:

4564

South Asian (SAS)

AF:

0.00

AC:

AN:

4192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64516

Other (OTH)

AF:

0.00

AC:

AN:

1886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.3

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.084

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.59

M_CAP

Benign

0.0014

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

PhyloP100

-2.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.85

Sift

Benign

0.037

Sift4G

Uncertain

0.016

Vest4

0.22

MVP

0.15

ClinPred

0.28

GERP RS

-3.8

gMVP

0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over