Variant chr19-11948323-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144566.3(ZNF700):c.299G>T(p.Cys100Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000734 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 0 hom. )

Consequence

ZNF700
NM_144566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.342

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06650779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF700	NM_144566.3 link	c.299G>T	p.Cys100Phe	missense_variant	4/4	ENST00000254321.10	NP_653167.1	Q9H0M5
ZNF700	NM_001271848.2 link	c.308G>T	p.Cys103Phe	missense_variant	4/4		NP_001258777.1	Q9H0M5A0A087WVH9
ZNF69	XM_017027231.2 link	c.500-31718G>T		intron_variant			XP_016882720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF700	ENST00000254321.10 link	c.299G>T	p.Cys100Phe	missense_variant	4/4	1	NM_144566.3	ENSP00000254321.4		Q9H0M5
ENSG00000267179	ENST00000590798.1 link	c.63+23050G>T		intron_variant		2		ENSP00000467286.1		F5H0A9

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000399

AC:

100

AN:

250916

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.000838

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000776

AC:

1134

AN:

1461502

Hom.:

Cov.:

AF XY:

0.000773

AC XY:

562

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000985

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000335

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000537

Hom.:

Bravo

AF:

0.000423

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00101

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

Sep 15, 2021

The c.299G>T (p.C100F) alteration is located in exon 4 (coding exon 4) of the ZNF700 gene. This alteration results from a G to T substitution at nucleotide position 299, causing the cysteine (C) at amino acid position 100 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.3

DANN

Benign

0.95

DEOGEN2

Benign

0.084

T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.045

T;T;T

M_CAP

Benign

0.00065

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

M;.;.

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-6.0

D;.;.

REVEL

Benign

0.13

Sift

Benign

0.060

T;.;.

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.12

MVP

0.27

MPC

0.0079

ClinPred

0.21

GERP RS

-0.55

Varity_R

0.11

gMVP

0.010

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