rs12486452

Positions:

• chr3-44283073-G-A

Variant summary

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

The NM_001145030.2(TOPAZ1):​c.3436+1042G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,896 control chromosomes in the GnomAD database, including 17,384 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 0.46 (17384 hom., cov: 31)
• Consequence: TOPAZ1 NM_001145030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPAZ1	NM_001145030.2	c.3436+1042G>A		intron_variant		ENST00000309765.4	NP_001138502.1
TOPAZ1	XM_011533694.3	c.3436+1042G>A		intron_variant			XP_011531996.1
TOPAZ1	XM_017006361.2	c.3436+1042G>A		intron_variant			XP_016861850.1
TOPAZ1	XM_017006362.1	c.3436+1042G>A		intron_variant			XP_016861851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPAZ1	ENST00000309765.4	c.3436+1042G>A		intron_variant		5	NM_001145030.2	ENSP00000310303	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70008 AN: 151778 Hom.: 17373 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.461 AC: 70051 AN: 151896 Hom.: 17384 Cov.: 31 AF XY: 0.471 AC XY: 34948 AN XY: 74216

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.461

Alfa AF: 0.451 Hom.: 2499

Bravo AF: 0.453

Asia WGS AF: 0.716 AC: 2485 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.42

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: rs12486452; hg19: chr3-44324565; COSMIC: COSV59070727;