Variant 15-43361137-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001372080.1(ZSCAN29):c.2495C>T(p.Ala832Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZSCAN29
NM_001372080.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.168

Variant links:

Genes affected

ZSCAN29 (HGNC:26673): (zinc finger and SCAN domain containing 29) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN29 links:

Genome browser will be placed here

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=0.15327737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN29	NM_001372080.1 linkuse as main transcript	c.2495C>T	p.Ala832Val	missense_variant	6/6	ENST00000684362.1	NP_001359009.1
ZSCAN29	NM_152455.4 linkuse as main transcript	c.2495C>T	p.Ala832Val	missense_variant	5/5		NP_689668.3	Q8IWY8-1Q96AG1Q05BJ4
ZSCAN29	XM_047432187.1 linkuse as main transcript	c.2495C>T	p.Ala832Val	missense_variant	6/6		XP_047288143.1
ZSCAN29	XM_047432188.1 linkuse as main transcript	c.1517C>T	p.Ala506Val	missense_variant	4/4		XP_047288144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN29	ENST00000684362.1 linkuse as main transcript	c.2495C>T	p.Ala832Val	missense_variant	6/6		NM_001372080.1	ENSP00000507363.1		Q8IWY8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.2495C>T (p.A832V) alteration is located in exon 5 (coding exon 5) of the ZSCAN29 gene. This alteration results from a C to T substitution at nucleotide position 2495, causing the alanine (A) at amino acid position 832 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.2

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.078

Sift

Benign

0.48

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.98

D;.

Vest4

0.060

MutPred

0.42

Loss of ubiquitination at K829 (P = 0.0455);.;

MVP

0.71

MPC

0.097

ClinPred

0.16

GERP RS

4.2

Varity_R

0.050

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over