chr3-44292607-T-C

Variant names:

• chr3-44292607-T-C
• rs1565215
• NM_001145030.2:c.3797+1721T>C

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+1721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,948 control chromosomes in the GnomAD database, including 18,198 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 0.48 (18198 hom., cov: 31)
• Consequence: TOPAZ1 NM_001145030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPAZ1	NM_001145030.2	MANE Select	c.3797+1721T>C		intron	N/A	NP_001138502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPAZ1	ENST00000309765.4	TSL:5 MANE Select	c.3797+1721T>C		intron	N/A	ENSP00000310303.4

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72492 AN: 151830 Hom.: 18183 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.477 AC: 72549 AN: 151948 Hom.: 18198 Cov.: 31 AF XY: 0.487 AC XY: 36116 AN XY: 74236

African (AFR) AF: 0.366 AC: 15143 AN: 41422

American (AMR) AF: 0.544 AC: 8311 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3464

East Asian (EAS) AF: 0.806 AC: 4162 AN: 5164

South Asian (SAS) AF: 0.703 AC: 3382 AN: 4814

European-Finnish (FIN) AF: 0.538 AC: 5661 AN: 10528

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32448 AN: 67972

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.471 Hom.: 3373

Bravo AF: 0.473

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-0.74
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: rs1565215; hg19: chr3-44334099;