rs1565214

Variant names:

• chr3-44292807-C-A
• rs1565214
• NM_001145030.2:c.3797+1921C>A

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+1921C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,036 control chromosomes in the GnomAD database, including 17,990 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 0.47 (17990 hom., cov: 32)
• Consequence: TOPAZ1 NM_001145030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPAZ1	NM_001145030.2	c.3797+1921C>A		intron_variant	Intron 12 of 19	ENST00000309765.4	NP_001138502.1
TOPAZ1	XM_011533694.3	c.3797+1921C>A		intron_variant	Intron 12 of 19		XP_011531996.1
TOPAZ1	XM_017006361.2	c.3797+1921C>A		intron_variant	Intron 12 of 17		XP_016861850.1
TOPAZ1	XM_017006362.1	c.3797+1921C>A		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+1921C>A		intron_variant	Intron 12 of 19	5	NM_001145030.2	ENSP00000310303.4

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71929 AN: 151918 Hom.: 17974 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.473 AC: 71985 AN: 152036 Hom.: 17990 Cov.: 32 AF XY: 0.483 AC XY: 35861 AN XY: 74294

African (AFR) AF: 0.351 AC: 14563 AN: 41470

American (AMR) AF: 0.543 AC: 8294 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.805 AC: 4171 AN: 5180

South Asian (SAS) AF: 0.703 AC: 3395 AN: 4826

European-Finnish (FIN) AF: 0.538 AC: 5676 AN: 10544

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32442 AN: 67954

Other (OTH) AF: 0.469 AC: 991 AN: 2112

Alfa AF: 0.472 Hom.: 2990

Bravo AF: 0.468

Asia WGS AF: 0.722 AC: 2510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.34
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: rs1565214; hg19: chr3-44334299;