Variant 19-53237000-G-A 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_182609.4(ZNF677):c.1727C>T(p.Thr576Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000598 in 1,571,480 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 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ZNF677
NM_182609.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.11

Variant links:

Genes affected

ZNF677 (HGNC:28730): (zinc finger protein 677) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF677 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=0.01217401).

BP6

Variant 19-53237000-G-A is Benign according to our data. Variant chr19-53237000-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2387627.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF677	NM_182609.4 linkuse as main transcript	c.1727C>T	p.Thr576Ile	missense_variant	5/5	ENST00000598513.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF677	ENST00000598513.6 linkuse as main transcript	c.1727C>T	p.Thr576Ile	missense_variant	5/5	1	NM_182609.4	P1
ZNF677	ENST00000333952.8 linkuse as main transcript	c.1727C>T	p.Thr576Ile	missense_variant	3/3	2		P1

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000131

AC:

AN:

214426

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

115446

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000179

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:

0.0000324

AC:

AN:

1419308

Hom.:

Cov.:

AF XY:

0.0000341

AC XY:

AN XY:

703576

show subpopulations

Gnomad4 AFR exome

AF:

0.000954

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.000315

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000276

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

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

Sep 16, 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

0.088

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.79

Cadd

Benign

3.2

Dann

Benign

0.68

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.000090

M_CAP

Benign

0.0021

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

Sift4G

Uncertain

0.019

D;D

Polyphen

0.028

B;B

Vest4

0.049

MVP

0.17

MPC

0.045

ClinPred

0.0048

GERP RS

0.18

Varity_R

0.029

gMVP

0.012

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