chr15-43361123-C-T

Position:

chr15-43361123-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001372080.1(ZSCAN29):c.2509G>A(p.Gly837Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,611,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

ZSCAN29
NM_001372080.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.258

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004167199).

BP6

Variant 15-43361123-C-T is Benign according to our data. Variant chr15-43361123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3057565.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZSCAN29	NM_001372080.1 linkuse as main transcript	c.2509G>A	p.Gly837Arg	missense_variant	6/6	ENST00000684362.1
ZSCAN29	NM_152455.4 linkuse as main transcript	c.2509G>A	p.Gly837Arg	missense_variant	5/5
ZSCAN29	XM_047432187.1 linkuse as main transcript	c.2509G>A	p.Gly837Arg	missense_variant	6/6
ZSCAN29	XM_047432188.1 linkuse as main transcript	c.1531G>A	p.Gly511Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN29	ENST00000684362.1 linkuse as main transcript	c.2509G>A	p.Gly837Arg	missense_variant	6/6		NM_001372080.1	P1	Q8IWY8-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

251024

Hom.:

AF XY:

0.000413

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000258

AC:

376

AN:

1459638

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

184

AN XY:

725620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00973

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.000846

GnomAD4 genome

AF:

0.000355

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000556

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ZSCAN29-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.8

DANN

Benign

0.45

DEOGEN2

Benign

0.0042

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.00060

LIST_S2

Benign

0.064

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

2.9

N;N

REVEL

Benign

0.049

Sift

Benign

0.87

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.10

MutPred

0.43

Gain of MoRF binding (P = 0.0218);.;

MVP

0.14

MPC

0.11

ClinPred

0.011

GERP RS

2.0

Varity_R

0.024

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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