20-49907751-A-C

Variant names:

• chr20-49907751-A-C
• rs636987
• NM_006038.4:c.336+404T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006038.4(SPATA2):​c.336+404T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 150,492 control chromosomes in the GnomAD database, including 15,792 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15792 hom., cov: 27)
• Consequence: SPATA2 NM_006038.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 5 publications found

Genes affected

SPATA2 (HGNC:14681): (spermatogenesis associated 2) Enables signaling receptor complex adaptor activity and ubiquitin-specific protease binding activity. Involved in several processes, including protein deubiquitination; regulation of necroptotic process; and regulation of tumor necrosis factor-mediated signaling pathway. Located in cytoplasm; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA2	NM_006038.4	c.336+404T>G		intron_variant	Intron 2 of 2	ENST00000289431.10	NP_006029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA2	ENST00000289431.10	c.336+404T>G		intron_variant	Intron 2 of 2	1	NM_006038.4	ENSP00000289431.5
SPATA2	ENST00000422556.1	c.336+404T>G		intron_variant	Intron 2 of 2	2		ENSP00000416799.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64580 AN: 150376 Hom.: 15774 Cov.: 27

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 64640 AN: 150492 Hom.: 15792 Cov.: 27 AF XY: 0.446 AC XY: 32662 AN XY: 73244

African (AFR) AF: 0.200 AC: 8228 AN: 41062

American (AMR) AF: 0.556 AC: 8315 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1320 AN: 3466

East Asian (EAS) AF: 0.786 AC: 3938 AN: 5010

South Asian (SAS) AF: 0.618 AC: 2943 AN: 4762

European-Finnish (FIN) AF: 0.621 AC: 6314 AN: 10168

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32233 AN: 67764

Other (OTH) AF: 0.443 AC: 926 AN: 2090

Alfa AF: 0.466 Hom.: 7682

Bravo AF: 0.413

Asia WGS AF: 0.665 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs636987; hg19: chr20-48524288;