rs13323323

Variant names:

• chr3-44291832-G-T
• rs13323323
• NM_001145030.2:c.3797+946G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TOPAZ1	NM_001145030.2	c.3797+946G>T		intron_variant	Intron 12 of 19	ENST00000309765.4	NP_001138502.1
TOPAZ1	XM_011533694.3	c.3797+946G>T		intron_variant	Intron 12 of 19		XP_011531996.1
TOPAZ1	XM_017006361.2	c.3797+946G>T		intron_variant	Intron 12 of 17		XP_016861850.1
TOPAZ1	XM_017006362.1	c.3797+946G>T		intron_variant	Intron 12 of 14		XP_016861851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOPAZ1	ENST00000309765.4	c.3797+946G>T		intron_variant	Intron 12 of 19	5	NM_001145030.2	ENSP00000310303.4

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

African (AFR) AF: 0.180 AC: 7480 AN: 41452

American (AMR) AF: 0.207 AC: 3168 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3468

East Asian (EAS) AF: 0.0424 AC: 219 AN: 5170

South Asian (SAS) AF: 0.256 AC: 1231 AN: 4806

European-Finnish (FIN) AF: 0.200 AC: 2107 AN: 10560

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16479 AN: 67976

Other (OTH) AF: 0.238 AC: 502 AN: 2112

Alfa AF: 0.228 Hom.: 6634

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
PhyloP100		0.81
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: rs13323323; hg19: chr3-44333324;