19-11948965-C-T

Variant summary

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

The NM_144566.3(ZNF700):c.941C>T(p.Ala314Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,608,434 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 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ZNF700
NM_144566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.909

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:

(HGNC:):

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=0.09521794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF700	NM_144566.3 linkuse as main transcript	c.941C>T	p.Ala314Val	missense_variant	4/4	ENST00000254321.10
ZNF700	NM_001271848.2 linkuse as main transcript	c.950C>T	p.Ala317Val	missense_variant	4/4
ZNF69	XM_017027231.2 linkuse as main transcript	c.500-31076C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF700	ENST00000254321.10 linkuse as main transcript	c.941C>T	p.Ala314Val	missense_variant	4/4	1	NM_144566.3	P2
	ENST00000586394.1 linkuse as main transcript	n.69-4017C>T		intron_variant, non_coding_transcript_variant		3
ZNF700	ENST00000622593.4 linkuse as main transcript	c.950C>T	p.Ala317Val	missense_variant	4/4	4		A2
ZNF700	ENST00000482090.1 linkuse as main transcript	c.887C>T	p.Ala296Val	missense_variant	3/3	2		A2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

244754

Hom.:

AF XY:

0.0000302

AC XY:

AN XY:

132376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000155

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:

0.0000179

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1456274

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

724376

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.000164

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:

0.0000432

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000902

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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 21, 2022

The c.941C>T (p.A314V) alteration is located in exon 4 (coding exon 4) of the ZNF700 gene. This alteration results from a C to T substitution at nucleotide position 941, causing the alanine (A) at amino acid position 314 to be replaced by a valine (V). 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

0.24

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.042

T;.;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.19

T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.095

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.5

D;.;.

REVEL

Benign

0.042

Sift

Benign

0.048

D;.;.

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.84

P;.;.

Vest4

0.098

MVP

0.17

MPC

0.037

ClinPred

0.32

GERP RS

0.67

Varity_R

0.085

gMVP

0.0079

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