Variant 1-247100961-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001142572.2(ZNF669):c.550A>G(p.Arg184Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,613,264 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

ZNF669
NM_001142572.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.520

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08733949).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF669	NM_001142572.2 linkuse as main transcript	c.550A>G	p.Arg184Gly	missense_variant	4/4	ENST00000448299.7	NP_001136044.1
ZNF669	NM_024804.3 linkuse as main transcript	c.808A>G	p.Arg270Gly	missense_variant	4/4		NP_079080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF669	ENST00000448299.7 linkuse as main transcript	c.550A>G	p.Arg184Gly	missense_variant	4/4	1	NM_001142572.2	ENSP00000404370	A2	Q96BR6-2
ZNF669	ENST00000343381.10 linkuse as main transcript	c.808A>G	p.Arg270Gly	missense_variant	4/4	1		ENSP00000342818	P2	Q96BR6-1
ZNF669	ENST00000366501.1 linkuse as main transcript	c.*360A>G		3_prime_UTR_variant	4/4	3		ENSP00000355457

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000240

AC:

AN:

250414

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

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:

0.000485

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000516

AC:

754

AN:

1460990

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

361

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000642

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000276

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

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

Aug 17, 2021

The c.808A>G (p.R270G) 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 808, causing the arginine (R) at amino acid position 270 to be replaced by a glycine (G). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.066

.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

0.57

D;D;D;D;N

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.99

.;D

Vest4

0.19

MVP

0.055

MPC

0.29

ClinPred

0.32

GERP RS

-1.1

Varity_R

0.48

gMVP

0.024

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