Genetic Variant SPATA31A7:p.Arg68Gln (chr9-61191466-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015667.2(SPATA31A7):c.203G>A(p.Arg68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,272,852 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 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. R68W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00052 ( 20 hom., cov: 17)

Exomes 𝑓: 0.00032 ( 99 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31A7
NM_015667.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

SPATA31A7 (HGNC:32007): (SPATA31 subfamily A member 7) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31A7 links:

ENSG00000304786 (HGNC:):

ENSG00000304786 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039848983).

BS2

High Homozygotes in GnomAdExome4 at 99 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A7	NM_015667.2 link	c.203G>A	p.Arg68Gln	missense_variant	Exon 2 of 4	ENST00000619167.2	NP_056482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31A7	ENST00000619167.2 link	c.203G>A	p.Arg68Gln	missense_variant	Exon 2 of 4	1	NM_015667.2	ENSP00000484807.1		Q8IWB4

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

116500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00248

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000438

Gnomad OTH

AF:

0.00319

GnomAD2 exomes

AF:

0.0000170

AC:

AN:

235084

AF XY:

0.0000235

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000315

AC:

401

AN:

1272852

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

180

AN XY:

631618

show subpopulations

African (AFR)

AF:

0.000200

AC:

AN:

25012

American (AMR)

AF:

0.00132

AC:

AN:

37900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22446

East Asian (EAS)

AF:

0.000156

AC:

AN:

32092

South Asian (SAS)

AF:

0.0000155

AC:

AN:

64566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47876

Middle Eastern (MID)

AF:

0.00126

AC:

AN:

3982

European-Non Finnish (NFE)

AF:

0.000290

AC:

286

AN:

987370

Other (OTH)

AF:

0.000949

AC:

AN:

51608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000523

AC:

AN:

116552

Hom.:

Cov.:

AF XY:

0.000586

AC XY:

AN XY:

56356

show subpopulations

African (AFR)

AF:

0.000107

AC:

AN:

27936

American (AMR)

AF:

0.00247

AC:

AN:

11324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2860

East Asian (EAS)

AF:

0.00

AC:

AN:

3270

South Asian (SAS)

AF:

0.00

AC:

AN:

2824

European-Finnish (FIN)

AF:

0.000114

AC:

AN:

8762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.000421

AC:

AN:

57028

Other (OTH)

AF:

0.00317

AC:

AN:

1576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000674

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.203G>A (p.R68Q) alteration is located in exon 2 (coding exon 2) of the SPATA31A7 gene. This alteration results from a G to A substitution at nucleotide position 203, causing the arginine (R) at amino acid position 68 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.7

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.022

LIST_S2

Benign

0.44

MetaRNN

Benign

0.040

PhyloP100

-1.5

Sift4G

Benign

0.42

Vest4

0.10

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Loading publications...

9-61191466-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over