rs9821268

Positions:

• chr3-44261632-A-G
• chr3-44261632-A-T

Variant summary

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

The NM_001145030.2(TOPAZ1):​c.2956-787A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,020 control chromosomes in the GnomAD database, including 18,236 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 (18236 hom., cov: 32)
• Consequence: TOPAZ1 NM_001145030.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.91).
• 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/exons	MANE	Protein	UniProt
TOPAZ1	NM_001145030.2	c.2956-787A>G		intron_variant		ENST00000309765.4	NP_001138502.1
TOPAZ1	XM_011533694.3	c.2956-787A>G		intron_variant			XP_011531996.1
TOPAZ1	XM_017006361.2	c.2956-787A>G		intron_variant			XP_016861850.1
TOPAZ1	XM_017006362.1	c.2956-787A>G		intron_variant			XP_016861851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPAZ1	ENST00000309765.4	c.2956-787A>G		intron_variant		5	NM_001145030.2	ENSP00000310303.4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72582 AN: 151902 Hom.: 18221 Cov.: 32

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: 0.701

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.478 AC: 72639 AN: 152020 Hom.: 18236 Cov.: 32 AF XY: 0.487 AC XY: 36192 AN XY: 74302

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.471

Alfa AF: 0.459 Hom.: 2147

Bravo AF: 0.473

Asia WGS AF: 0.723 AC: 2515 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	3.4
DANN	Benign	0.54

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: rs9821268; hg19: chr3-44303124;