3-44257713-C-T

Variant names:

• chr3-44257713-C-T
• rs7631790
• NM_001145030.2:c.2955+1435C>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.2955+1435C>T 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 151,366 control chromosomes in the GnomAD database, including 17,323 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 (17323 hom., cov: 29)
• Consequence: TOPAZ1 NM_001145030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145030.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPAZ1	NM_001145030.2	MANE Select	c.2955+1435C>T		intron	N/A	NP_001138502.1	Q8N9V7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPAZ1	ENST00000309765.4	TSL:5 MANE Select	c.2955+1435C>T		intron	N/A	ENSP00000310303.4	Q8N9V7

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69794 AN: 151248 Hom.: 17312 Cov.: 29

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.513

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: 69837 AN: 151366 Hom.: 17323 Cov.: 29 AF XY: 0.471 AC XY: 34834 AN XY: 73924

African (AFR) AF: 0.309 AC: 12746 AN: 41214

American (AMR) AF: 0.538 AC: 8162 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1839 AN: 3466

East Asian (EAS) AF: 0.805 AC: 4145 AN: 5146

South Asian (SAS) AF: 0.705 AC: 3379 AN: 4796

European-Finnish (FIN) AF: 0.539 AC: 5623 AN: 10430

Middle Eastern (MID) AF: 0.524 AC: 151 AN: 288

European-Non Finnish (NFE) AF: 0.477 AC: 32369 AN: 67834

Other (OTH) AF: 0.461 AC: 971 AN: 2108

Alfa AF: 0.444 Hom.: 2498

Bravo AF: 0.453

Asia WGS AF: 0.718 AC: 2495 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		0.19
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: rs7631790; hg19: chr3-44299205;