Variant 19-22180593-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001001411.3(ZNF676):c.1124G>A(p.Ser375Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,611,188 control chromosomes in the GnomAD database, including 3 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

ZNF676
NM_001001411.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -9.11

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011120796).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF676	NM_001001411.3 linkuse as main transcript	c.1124G>A	p.Ser375Asn	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.1124G>A	p.Ser375Asn	missense_variant	3/3	2	NM_001001411.3	ENSP00000380310.1		Q8N7Q3
ZNF676	ENST00000650058.1 linkuse as main transcript	c.1220G>A	p.Ser407Asn	missense_variant	4/4			ENSP00000497897.1		A0A3B3ITU2

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

159

AN:

149382

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00350

Gnomad NFE

AF:

0.00130

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000737

AC:

183

AN:

248390

Hom.:

AF XY:

0.000794

AC XY:

107

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

797

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00106

AC:

159

AN:

149500

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

72998

show subpopulations

Gnomad4 AFR

AF:

0.000197

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00130

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.000833

Hom.:

Bravo

AF:

0.000982

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.00129

AC:

ExAC

AF:

0.000611

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 19, 2022

The c.1124G>A (p.S375N) alteration is located in exon 3 (coding exon 3) of the ZNF676 gene. This alteration results from a G to A substitution at nucleotide position 1124, causing the serine (S) at amino acid position 375 to be replaced by an asparagine (N). 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

0.19

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.011

DANN

Benign

0.20

DEOGEN2

Benign

0.0021

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00042

LIST_S2

Benign

0.035

.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

1.7

N;.

REVEL

Benign

0.047

Sift

Benign

1.0

T;.

Sift4G

Benign

0.59

T;.

Polyphen

0.98

D;.

Vest4

0.040

MVP

0.43

MPC

0.022

ClinPred

0.030

GERP RS

-0.53

Varity_R

0.028

gMVP

0.0038

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