3-44243092-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145030.2(TOPAZ1):​c.586G>C​(p.Val196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V196I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

TOPAZ1
NM_001145030.2 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09577626).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOPAZ1NM_001145030.2 linkc.586G>C p.Val196Leu missense_variant Exon 2 of 20 ENST00000309765.4 NP_001138502.1 Q8N9V7
TOPAZ1XM_011533694.3 linkc.586G>C p.Val196Leu missense_variant Exon 2 of 20 XP_011531996.1
TOPAZ1XM_017006361.2 linkc.586G>C p.Val196Leu missense_variant Exon 2 of 18 XP_016861850.1
TOPAZ1XM_017006362.1 linkc.586G>C p.Val196Leu missense_variant Exon 2 of 15 XP_016861851.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOPAZ1ENST00000309765.4 linkc.586G>C p.Val196Leu missense_variant Exon 2 of 20 5 NM_001145030.2 ENSP00000310303.4 Q8N9V7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.096
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.027
Sift
Uncertain
0.012
D
Sift4G
Uncertain
0.059
T
Polyphen
0.59
P
Vest4
0.26
MutPred
0.23
Gain of helix (P = 0.0199);
MVP
0.076
ClinPred
0.26
T
GERP RS
3.0
Varity_R
0.093
gMVP
0.13

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: rs9284879; hg19: chr3-44284584; API