rs1252937966

Variant names:

• chr9-81932302-A-G
• rs1252937966
• NM_001145197.1:c.2141A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001145197.1(SPATA31D4):​c.2141A>G​(p.Asn714Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 8)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52
• Publications: 0 publications found

Genes affected

SPATA31D4 (HGNC:38601): (SPATA31 subfamily D member 4) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267559 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030048192).
• BP6: Variant 9-81932302-A-G is Benign according to our data. Variant chr9-81932302-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2469748.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145197.1. 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
	SPATA31D4	NM_001145197.1	MANE Select	c.2141A>G	p.Asn714Ser	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
	LOC105376105	NR_188610.1		n.1040-908T>C		intron	N/A
	LOC105376105	NR_188611.1		n.1229-908T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2141A>G	p.Asn714Ser	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-908T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 59396 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000269 AC: 2 AN: 74330 AF XY: 0.0000261

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000227

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000136 AC: 12 AN: 882110 Hom.: 0 Cov.: 13 AF XY: 0.0000135 AC XY: 6 AN XY: 444212

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

African (AFR) AF: 0.00 AC: 0 AN: 20850

American (AMR) AF: 0.00 AC: 0 AN: 27570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18904

East Asian (EAS) AF: 0.0000896 AC: 3 AN: 33474

South Asian (SAS) AF: 0.00 AC: 0 AN: 61698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2946

European-Non Finnish (NFE) AF: 0.0000141 AC: 9 AN: 638866

Other (OTH) AF: 0.00 AC: 0 AN: 40040

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000724364), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 59396 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 27700

African (AFR) AF: 0.00 AC: 0 AN: 15312

American (AMR) AF: 0.00 AC: 0 AN: 5466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1740

East Asian (EAS) AF: 0.00 AC: 0 AN: 2594

South Asian (SAS) AF: 0.00 AC: 0 AN: 1592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28290

Other (OTH) AF: 0.00 AC: 0 AN: 726

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.45
DEOGEN2	Benign	0.00077	T
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.030	T
MutationAssessor	Benign	-1.3	N
PhyloP100		-2.5
PrimateAI	Uncertain	0.54	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.014
GERP RS		0.67
Varity_R		0.10
gMVP		0.015
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1252937966; hg19: chr9-84547217;