Variant 19-37347220-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001353803.2(ZNF875):c.64T>G(p.Tyr22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,614,110 control chromosomes in the GnomAD database, including 305 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 0.025 ( 176 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 129 hom. )

Consequence

ZNF875
NM_001353803.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.154

Variant links:

Genes affected

ZNF875 (HGNC:4928): (zinc finger protein 875) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF875 links:

ZNF875 (HGNC:):

ZNF875 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030048192).

BP6

Variant 19-37347220-T-G is Benign according to our data. Variant chr19-37347220-T-G is described in ClinVar as [Benign]. Clinvar id is 787489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF875	NM_001353803.2 linkuse as main transcript	c.64T>G	p.Tyr22Asp	missense_variant	3/5	ENST00000392153.8	NP_001340732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF875	ENST00000392153.8 linkuse as main transcript	c.64T>G	p.Tyr22Asp	missense_variant	3/5	1	NM_001353803.2	ENSP00000375994.3		P10072-2

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3753

AN:

152140

Hom.:

176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0852

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00687

AC:

1727

AN:

251454

Hom.:

AF XY:

0.00502

AC XY:

682

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.00607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00248

AC:

3622

AN:

1461852

Hom.:

129

Cov.:

AF XY:

0.00208

AC XY:

1514

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.00673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.00520

GnomAD4 genome

AF:

0.0246

AC:

3753

AN:

152258

Hom.:

176

Cov.:

AF XY:

0.0240

AC XY:

1785

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0850

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0286

ESP6500AA

AF:

0.0869

AC:

383

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00830

AC:

1008

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.015

.;.;T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.0069

T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.94

.;.;N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

2.8

N;.;N;.

REVEL

Benign

0.074

Sift

Benign

0.32

T;.;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.27

MVP

0.17

MPC

0.042

ClinPred

0.0073

GERP RS

3.4

Varity_R

0.052

gMVP

0.090

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