Genetic Variant NM_207416.3:c.2340C>A (chr9-81947593-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207416.3(SPATA31D3):c.2340C>A(p.Asn780Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000077 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D3
NM_207416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.77

Publications

1 publications found

Variant links:

Genes affected

SPATA31D3 (HGNC:38603): (SPATA31 subfamily D member 3) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31D3 links:

ENSG00000267559 (HGNC:):

ENSG00000267559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035232246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA31D3	NM_207416.3	MANE Select	c.2340C>A	p.Asn780Lys	missense	Exon 4 of 4	NP_997299.2	P0C874
LOC105376105	NR_188610.1		n.943-1107G>T		intron	N/A
LOC105376105	NR_188611.1		n.943-1107G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPATA31D3	ENST00000445385.3	TSL:1 MANE Select	c.2340C>A	p.Asn780Lys	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
ENSG00000267559	ENST00000585776.5	TSL:2	n.943-1107G>T		intron	N/A
ENSG00000267559	ENST00000592744.1	TSL:4	n.519-1107G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000424

AC:

AN:

236092

AF XY:

0.00000778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000927

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000770

AC:

AN:

1428182

Hom.:

Cov.:

AF XY:

0.00000844

AC XY:

AN XY:

710504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31694

American (AMR)

AF:

0.00

AC:

AN:

41240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25696

East Asian (EAS)

AF:

0.00

AC:

AN:

38132

South Asian (SAS)

AF:

0.00

AC:

AN:

84308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

1089734

Other (OTH)

AF:

0.00

AC:

AN:

59150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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

Cov.:

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

0.14

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.014

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0076

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.28

MetaRNN

Benign

0.035

MutationAssessor

Benign

1.0

PhyloP100

-2.8

PrimateAI

Benign

0.41

Sift4G

Benign

0.26

Polyphen

0.050

Vest4

0.037

GERP RS

-1.4

Varity_R

0.046

gMVP

0.034

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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