rs9821268

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.335
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]

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ACMG classification

Classification made for transcript

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
TOPAZ1NM_001145030.2 linkuse as main transcriptc.2956-787A>G intron_variant ENST00000309765.4 NP_001138502.1
TOPAZ1XM_011533694.3 linkuse as main transcriptc.2956-787A>G intron_variant XP_011531996.1
TOPAZ1XM_017006361.2 linkuse as main transcriptc.2956-787A>G intron_variant XP_016861850.1
TOPAZ1XM_017006362.1 linkuse as main transcriptc.2956-787A>G intron_variant XP_016861851.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TOPAZ1ENST00000309765.4 linkuse as main transcriptc.2956-787A>G intron_variant 5 NM_001145030.2 ENSP00000310303 P1

Frequencies

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

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

Other links and lift over

dbSNP: rs9821268; hg19: chr3-44303124; API