NM_006038.4:c.*1546T>C

Variant names:

• chr20-49904073-A-G
• rs632376
• NM_006038.4:c.*1546T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.74).
• 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 rank	MANE	Protein	UniProt
SPATA2	NM_006038.4	c.*1546T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000289431.10	NP_006029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA2	ENST00000289431.10	c.*1546T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_006038.4	ENSP00000289431.5
SPATA2	ENST00000422556.1	c.*1546T>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000416799.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.580 AC: 240 AN: 414

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.0774 AC: 3200 AN: 41354

American (AMR) AF: 0.436 AC: 6611 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1775 AN: 5156

South Asian (SAS) AF: 0.558 AC: 2689 AN: 4818

European-Finnish (FIN) AF: 0.564 AC: 5899 AN: 10454

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28586 AN: 67810

Other (OTH) AF: 0.343 AC: 723 AN: 2106

Alfa AF: 0.348 Hom.: 2625

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
PhyloP100		0.52
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: rs632376; hg19: chr20-48520610; COSMIC: COSV56868932;