rs13323323

chr3-44291832-G-T

Variant summary

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

The NM_001145030.2(TOPAZ1):c.3797+946G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,030 control chromosomes in the GnomAD database, including 3,696 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 0.22 (3696 hom., cov: 32)
• Consequence: TOPAZ1 NM_001145030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

Genes affected

TOPAZ1 (HGNC:24746): (testis and ovary specific TOPAZ 1) Predicted to be involved in spermatid development and spermatocyte division. Predicted to act upstream of or within apoptotic process; ncRNA transcription; and positive regulation of meiotic cell cycle phase transition. Predicted to be located in cytosol. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOPAZ1	NM_001145030.2	c.3797+946G>T		intron_variant		ENST00000309765.4
TOPAZ1	XM_011533694.3	c.3797+946G>T		intron_variant
TOPAZ1	XM_017006361.2	c.3797+946G>T		intron_variant
TOPAZ1	XM_017006362.1	c.3797+946G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOPAZ1	ENST00000309765.4	c.3797+946G>T		intron_variant		5	NM_001145030.2	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32726 AN: 151912 Hom.: 3698 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.215 AC: 32735 AN: 152030 Hom.: 3696 Cov.: 32 AF XY: 0.211 AC XY: 15710 AN XY: 74282

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.238

Alfa AF: 0.221 Hom.: 484

Bravo AF: 0.215

Asia WGS AF: 0.130 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	10
Dann	Benign	0.83

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: rs13323323; hg19: chr3-44333324;