Variant chr19-36877633-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001242472.2(ZNF345):c.803G>C(p.Ser268Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,614,112 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 8 hom., cov: 33)

Exomes 𝑓: 0.011 ( 119 hom. )

Consequence

ZNF345
NM_001242472.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

ZNF345 (HGNC:16367): (zinc finger protein 345) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF345 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00494498).

BP6

Variant 19-36877633-G-C is Benign according to our data. Variant chr19-36877633-G-C is described in ClinVar as [Benign]. Clinvar id is 789119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF345	NM_001242472.2 linkuse as main transcript	c.803G>C	p.Ser268Thr	missense_variant	3/3	ENST00000420450.6	NP_001229401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF345	ENST00000420450.6 linkuse as main transcript	c.803G>C	p.Ser268Thr	missense_variant	3/3	1	NM_001242472.2	ENSP00000431216	P1

Frequencies

GnomAD3 genomes

AF:

0.00757

AC:

1152

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00698

AC:

1753

AN:

251106

Hom.:

AF XY:

0.00708

AC XY:

961

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00671

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0110

AC:

16086

AN:

1461878

Hom.:

119

Cov.:

AF XY:

0.0106

AC XY:

7715

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00693

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.00384

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00756

AC:

1151

AN:

152234

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

523

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00958

Hom.:

Bravo

AF:

0.00841

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.00698

AC:

847

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0111

EpiControl

AF:

0.0121

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.4

DANN

Benign

0.79

DEOGEN2

Benign

0.037

T;T;T;T;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.54

.;.;.;.;T;T

MetaRNN

Benign

0.0049

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.15

N;N;N;N;N;.

MutationTaster

Benign

0.80

D;N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

.;.;N;N;.;.

REVEL

Benign

0.060

Sift

Benign

0.38

.;.;T;T;.;.

Sift4G

Benign

0.27

T;T;T;T;T;.

Polyphen

0.0

B;B;B;B;B;.

Vest4

0.094

MVP

0.40

MPC

0.13

ClinPred

0.00031

GERP RS

1.6

Varity_R

0.047

gMVP

0.015

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.

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