chr20-49904073-A-G

Position:

• chr20-49904073-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006038.4(SPATA2):​c.*1546T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,962 control chromosomes in the GnomAD database, including 10,870 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 0.34 (10804 hom., cov: 29)
  • Exomes 𝑓: 0.57 (66 hom.)
• Consequence: SPATA2 NM_006038.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA2	NM_006038.4	c.*1546T>C		3_prime_UTR_variant	3/3	ENST00000289431.10	NP_006029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA2	ENST00000289431.10	c.*1546T>C		3_prime_UTR_variant	3/3	1	NM_006038.4	ENSP00000289431	P1
SPATA2	ENST00000422556.1	c.*1546T>C		3_prime_UTR_variant	3/3	2		ENSP00000416799	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 50965 AN: 151424 Hom.: 10792 Cov.: 29

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.574 AC: 241 AN: 420 Hom.: 66 Cov.: 0 AF XY: 0.587 AC XY: 149 AN XY: 254

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.336 AC: 50986 AN: 151542 Hom.: 10804 Cov.: 29 AF XY: 0.351 AC XY: 25959 AN XY: 74016

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.343

Alfa AF: 0.280 Hom.: 880

Bravo AF: 0.308

Asia WGS AF: 0.453 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.0
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs632376; hg19: chr20-48520610; COSMIC: COSV56868932;