Variant 15-43361800-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001372080.1(ZSCAN29):c.1832G>A(p.Cys611Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZSCAN29
NM_001372080.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.758

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02754888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZSCAN29	NM_001372080.1 linkuse as main transcript	c.1832G>A	p.Cys611Tyr	missense_variant	6/6	ENST00000684362.1
ZSCAN29	NM_152455.4 linkuse as main transcript	c.1832G>A	p.Cys611Tyr	missense_variant	5/5
ZSCAN29	XM_047432187.1 linkuse as main transcript	c.1832G>A	p.Cys611Tyr	missense_variant	6/6
ZSCAN29	XM_047432188.1 linkuse as main transcript	c.854G>A	p.Cys285Tyr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN29	ENST00000684362.1 linkuse as main transcript	c.1832G>A	p.Cys611Tyr	missense_variant	6/6		NM_001372080.1	P1	Q8IWY8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251444

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000494

AC:

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

Dec 19, 2022

The c.1832G>A (p.C611Y) alteration is located in exon 5 (coding exon 5) of the ZSCAN29 gene. This alteration results from a G to A substitution at nucleotide position 1832, causing the cysteine (C) at amino acid position 611 to be replaced by a tyrosine (Y). 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

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.67

Cadd

Benign

0.16

Dann

Benign

0.24

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00067

LIST_S2

Benign

0.14

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

N;D

REVEL

Benign

0.015

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.012

B;.

Vest4

0.14

MutPred

0.40

Gain of phosphorylation at C611 (P = 0.011);.;

MVP

0.11

MPC

0.16

ClinPred

0.014

GERP RS

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.089

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

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