rs1435078723

Variant names:

• chr9-81947384-C-T
• rs1435078723
• NM_207416.3:c.2131C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207416.3(SPATA31D3):​c.2131C>T​(p.Arg711Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 9)
  • Exomes 𝑓: 0.000032 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.66
• Publications: 0 publications found

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]

ENSG00000267559 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.064257234).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D3	NM_207416.3	MANE Select	c.2131C>T	p.Arg711Cys	missense	Exon 4 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.943-898G>A		intron	N/A
	LOC105376105	NR_188611.1		n.943-898G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D3	ENST00000445385.3	TSL:1 MANE Select	c.2131C>T	p.Arg711Cys	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.943-898G>A		intron	N/A
	ENSG00000267559	ENST00000592744.1	TSL:4	n.519-898G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000429 AC: 29 AN: 67664 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000165

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: 0.000108 AC: 8 AN: 73920 AF XY: 0.0000798

Gnomad AFR exome AF: 0.00109

Gnomad AMR exome AF: 0.0000668

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000361

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000317 AC: 28 AN: 883740 Hom.: 1 Cov.: 13 AF XY: 0.0000292 AC XY: 13 AN XY: 445926

African (AFR) AF: 0.000529 AC: 11 AN: 20800

American (AMR) AF: 0.0000729 AC: 2 AN: 27420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18730

East Asian (EAS) AF: 0.00 AC: 0 AN: 31744

South Asian (SAS) AF: 0.0000171 AC: 1 AN: 58338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2948

European-Non Finnish (NFE) AF: 0.0000202 AC: 13 AN: 642534

Other (OTH) AF: 0.0000249 AC: 1 AN: 40218

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000429 AC: 29 AN: 67664 Hom.: 0 Cov.: 9 AF XY: 0.000256 AC XY: 8 AN XY: 31274

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

African (AFR) AF: 0.00167 AC: 28 AN: 16772

American (AMR) AF: 0.000165 AC: 1 AN: 6070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1838

East Asian (EAS) AF: 0.00 AC: 0 AN: 1678

South Asian (SAS) AF: 0.00 AC: 0 AN: 1268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34002

Other (OTH) AF: 0.00 AC: 0 AN: 778

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000594053), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.10
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.9
DANN	Benign	0.64
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.064	T
MutationAssessor	Benign	0.83	L
PhyloP100		-4.7
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.086	T
Polyphen		1.0	D
Vest4		0.045
GERP RS		-4.3
Varity_R		0.092
gMVP		0.035
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: rs1435078723; hg19: chr9-84562299;