chr19-11948537-T-G

Position:

chr19-11948537-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000254321.10(ZNF700):c.513T>G(p.Asn171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,610,414 control chromosomes in the GnomAD database, including 1 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 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

ZNF700
ENST00000254321.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08032459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF700	NM_144566.3 linkuse as main transcript	c.513T>G	p.Asn171Lys	missense_variant	4/4	ENST00000254321.10	NP_653167.1	Q9H0M5
ZNF700	NM_001271848.2 linkuse as main transcript	c.522T>G	p.Asn174Lys	missense_variant	4/4		NP_001258777.1	Q9H0M5A0A087WVH9
ZNF69	XM_017027231.2 linkuse as main transcript	c.500-31504T>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.513T>G	p.Asn171Lys	missense_variant	4/4	1	NM_144566.3	ENSP00000254321.4		Q9H0M5
ENSG00000267179	ENST00000590798.1 linkuse as main transcript	c.63+23264T>G		intron_variant		2		ENSP00000467286.1		F5H0A9

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

247326

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

133702

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

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:

0.000275

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000443

AC:

646

AN:

1458284

Hom.:

Cov.:

AF XY:

0.000427

AC XY:

310

AN XY:

725416

show subpopulations

Gnomad4 AFR exome

AF:

0.0000605

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000571

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000171

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

Dec 06, 2022

The c.513T>G (p.N171K) alteration is located in exon 4 (coding exon 4) of the ZNF700 gene. This alteration results from a T to G substitution at nucleotide position 513, causing the asparagine (N) at amino acid position 171 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.2

DANN

Benign

0.94

DEOGEN2

Benign

0.00091

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.000040

LIST_S2

Benign

0.14

T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.23

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

N;.;.

REVEL

Benign

0.034

Sift

Benign

0.044

D;.;.

Sift4G

Benign

0.93

T;T;T

Polyphen

0.0030

B;.;.

Vest4

0.25

MutPred

0.54

Gain of solvent accessibility (P = 4e-04);.;.;

MVP

0.31

MPC

0.016

ClinPred

0.048

GERP RS

0.60

Varity_R

0.085

gMVP

0.0027

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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