Variant chr19-11948985-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000254321.10(ZNF700):c.961C>G(p.Leu321Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000737 in 1,608,426 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 11 hom. )

Consequence

ZNF700
ENST00000254321.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

ZNF700 (HGNC:25292): (zinc finger protein 700) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF700 links:

ENSG00000267179 (HGNC:):

ENSG00000267179 links:

ZNF69 (HGNC:13138): (zinc finger protein 69) Enables identical protein 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]

ZNF69 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=0.0059915185).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF700	NM_144566.3 linkuse as main transcript	c.961C>G	p.Leu321Val	missense_variant	4/4	ENST00000254321.10	NP_653167.1	Q9H0M5
ZNF700	NM_001271848.2 linkuse as main transcript	c.970C>G	p.Leu324Val	missense_variant	4/4		NP_001258777.1	Q9H0M5A0A087WVH9
ZNF69	XM_017027231.2 linkuse as main transcript	c.500-31056C>G		intron_variant			XP_016882720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF700	ENST00000254321.10 linkuse as main transcript	c.961C>G	p.Leu321Val	missense_variant	4/4	1	NM_144566.3	ENSP00000254321.4		Q9H0M5
ENSG00000267179	ENST00000590798.1 linkuse as main transcript	c.63+23712C>G		intron_variant		2		ENSP00000467286.1		F5H0A9

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

595

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000952

AC:

233

AN:

244820

Hom.:

AF XY:

0.000695

AC XY:

AN XY:

132450

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.000217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.000836

GnomAD4 exome

AF:

0.000405

AC:

590

AN:

1456148

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

247

AN XY:

724226

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.000305

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000814

GnomAD4 genome

AF:

0.00391

AC:

595

AN:

152278

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

290

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000590

Hom.:

Bravo

AF:

0.00429

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00114

AC:

139

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.071

DANN

Benign

0.79

DEOGEN2

Benign

0.062

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.36

T;T;T

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.90

N;.;.

REVEL

Benign

0.074

Sift

Benign

0.18

T;.;.

Sift4G

Uncertain

0.045

D;D;D

Polyphen

0.0

B;.;.

Vest4

0.056

MVP

0.16

MPC

0.0083

ClinPred

0.011

GERP RS

-0.97

Varity_R

0.022

gMVP

0.013

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over