Variant 3-44242333-T-TCGTCAGACC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_001145030.2(TOPAZ1):c.283_291dupTCAGACCCG(p.Ser95_Pro97dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000826 in 1,552,160 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 8 hom. )

Consequence

TOPAZ1
NM_001145030.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.977

Variant links:

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]

TOPAZ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001145030.2.

BP6

Variant 3-44242333-T-TCGTCAGACC is Benign according to our data. Variant chr3-44242333-T-TCGTCAGACC is described in ClinVar as [Benign]. Clinvar id is 787014.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPAZ1	NM_001145030.2 linkuse as main transcript	c.283_291dupTCAGACCCG	p.Ser95_Pro97dup	conservative_inframe_insertion	1/20	ENST00000309765.4	NP_001138502.1	Q8N9V7
TOPAZ1	XM_011533694.3 linkuse as main transcript	c.283_291dupTCAGACCCG	p.Ser95_Pro97dup	conservative_inframe_insertion	1/20		XP_011531996.1
TOPAZ1	XM_017006361.2 linkuse as main transcript	c.283_291dupTCAGACCCG	p.Ser95_Pro97dup	conservative_inframe_insertion	1/18		XP_016861850.1
TOPAZ1	XM_017006362.1 linkuse as main transcript	c.283_291dupTCAGACCCG	p.Ser95_Pro97dup	conservative_inframe_insertion	1/15		XP_016861851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPAZ1	ENST00000309765.4 linkuse as main transcript	c.283_291dupTCAGACCCG	p.Ser95_Pro97dup	conservative_inframe_insertion	1/20	5	NM_001145030.2	ENSP00000310303.4		Q8N9V7

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

622

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00106

AC:

167

AN:

157526

Hom.:

AF XY:

0.000867

AC XY:

AN XY:

83086

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000919

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000494

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000471

AC:

659

AN:

1399924

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

288

AN XY:

690450

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000538

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00409

AC:

623

AN:

152236

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00273

Hom.:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over