Variant 1-247101128-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000448299.7(ZNF669):c.383A>G(p.Tyr128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ZNF669
ENST00000448299.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

ZNF669 (HGNC:25736): (zinc finger protein 669) 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]

ZNF669 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=0.08362946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF669	NM_001142572.2 linkuse as main transcript	c.383A>G	p.Tyr128Cys	missense_variant	4/4	ENST00000448299.7	NP_001136044.1	Q96BR6-2
ZNF669	NM_024804.3 linkuse as main transcript	c.641A>G	p.Tyr214Cys	missense_variant	4/4		NP_079080.2	Q96BR6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF669	ENST00000448299.7 linkuse as main transcript	c.383A>G	p.Tyr128Cys	missense_variant	4/4	1	NM_001142572.2	ENSP00000404370.2	Q96BR6-2
ZNF669	ENST00000343381.10 linkuse as main transcript	c.641A>G	p.Tyr214Cys	missense_variant	4/4	1		ENSP00000342818.6	Q96BR6-1
ZNF669	ENST00000366500.5 linkuse as main transcript	c.*106A>G		3_prime_UTR_variant	3/3	3		ENSP00000355456.1	Q5VT37
ZNF669	ENST00000366501.1 linkuse as main transcript	c.*193A>G		3_prime_UTR_variant	4/4	3		ENSP00000355457.1	Q5VT36

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251332

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

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

Jan 23, 2023

The c.641A>G (p.Y214C) alteration is located in exon 4 (coding exon 4) of the ZNF669 gene. This alteration results from a A to G substitution at nucleotide position 641, causing the tyrosine (Y) at amino acid position 214 to be replaced by a cysteine (C). 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

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.039

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.038

D;D

Polyphen

0.011

.;B

Vest4

0.23

MutPred

0.49

.;Loss of solvent accessibility (P = 0.0022);

MVP

0.055

MPC

0.078

ClinPred

0.061

GERP RS

-0.55

Varity_R

0.17

gMVP

0.036

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