1-162373984-A-G

Position:

• chr1-162373984-A-G

Variant summary

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

The NM_182581.4(SPATA46):​c.*64T>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 0.405 in 1,494,302 control chromosomes in the GnomAD database, including 125,032 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 0.37 (11151 hom., cov: 33)
  • Exomes 𝑓: 0.41 (113881 hom.)
• Consequence: SPATA46 NM_182581.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

Genes affected

SPATA46 (HGNC:27648): (spermatogenesis associated 46) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization and spermatogenesis. Predicted to be active in nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254706 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA46	NM_182581.4	c.*64T>C		3_prime_UTR_variant	3/3	ENST00000367935.10	NP_872387.2
SPATA46	XM_005245103.4	c.*64T>C		3_prime_UTR_variant	2/2		XP_005245160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA46	ENST00000367935.10	c.*64T>C		3_prime_UTR_variant	3/3	1	NM_182581.4	ENSP00000356912.4
ENSG00000254706	ENST00000420220.1	c.-12+6780A>G		intron_variant		5		ENSP00000398035.1
ENSG00000254706	ENST00000431696.1	c.226+6780A>G		intron_variant		4		ENSP00000405676.2
ENSG00000254706	ENST00000367932.3	n.152+6521A>G		intron_variant		4		ENSP00000356909.3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55980 AN: 152050 Hom.: 11133 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.409 AC: 548433 AN: 1342134 Hom.: 113881 Cov.: 24 AF XY: 0.406 AC XY: 267583 AN XY: 658416

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.368 AC: 56022 AN: 152168 Hom.: 11151 Cov.: 33 AF XY: 0.372 AC XY: 27693 AN XY: 74392

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.368

Alfa AF: 0.397 Hom.: 12235

Bravo AF: 0.360

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.73

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: rs7512126; hg19: chr1-162343774; COSMIC: COSV62634956; COSMIC: COSV62634956;