Variant 19-22180206-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001001411.3(ZNF676):c.1511G>C(p.Arg504Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 133,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF676
NM_001001411.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

ZNF676 (HGNC:20429): (zinc finger protein 676) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF676 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=0.011954904).

BP6

Variant 19-22180206-C-G is Benign according to our data. Variant chr19-22180206-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2380097.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF676	NM_001001411.3 linkuse as main transcript	c.1511G>C	p.Arg504Pro	missense_variant	3/3	ENST00000397121.3	NP_001001411.2	Q8N7Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF676	ENST00000397121.3 linkuse as main transcript	c.1511G>C	p.Arg504Pro	missense_variant	3/3	2	NM_001001411.3	ENSP00000380310.1		Q8N7Q3
ZNF676	ENST00000650058.1 linkuse as main transcript	c.1607G>C	p.Arg536Pro	missense_variant	4/4			ENSP00000497897.1		A0A3B3ITU2

Frequencies

GnomAD3 genomes

AF:

0.000194

AC:

AN:

133832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000741

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00138

Gnomad SAS

AF:

0.000244

Gnomad FIN

AF:

0.000112

Gnomad MID

AF:

0.00515

Gnomad NFE

AF:

0.0000487

Gnomad OTH

AF:

0.000552

GnomAD3 exomes

AF:

0.0000297

AC:

AN:

235812

Hom.:

AF XY:

0.0000313

AC XY:

AN XY:

127906

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.0000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000358

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000194

AC:

AN:

1444182

Hom.:

Cov.:

AF XY:

0.0000237

AC XY:

AN XY:

718222

show subpopulations

Gnomad4 AFR exome

AF:

0.000215

Gnomad4 AMR exome

AF:

0.0000955

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0000358

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000194

AC:

AN:

133930

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

65504

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.0000741

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00139

Gnomad4 SAS

AF:

0.000245

Gnomad4 FIN

AF:

0.000112

Gnomad4 NFE

AF:

0.0000487

Gnomad4 OTH

AF:

0.000546

Alfa

AF:

0.000430

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.26

DANN

Benign

0.23

DEOGEN2

Benign

0.0015

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.050

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.0

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

5.8

N;.

REVEL

Benign

0.028

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0020

B;.

Vest4

0.10

MVP

0.10

MPC

0.026

ClinPred

0.013

GERP RS

-1.6

Varity_R

0.059

gMVP

0.021

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