Variant 19-51891291-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_023074.4(ZNF649):c.845G>A(p.Arg282Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0000066 ( 0 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

ZNF649
NM_023074.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.46

Variant links:

Genes affected

ZNF649 (HGNC:25741): (zinc finger protein 649) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription, DNA-templated. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF649 links:

ZNF649-AS1 (HGNC:51285): (ZNF649 antisense RNA 1)

ZNF649-AS1 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=0.09158096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF649	NM_023074.4 linkuse as main transcript	c.845G>A	p.Arg282Lys	missense_variant	5/5	ENST00000354957.8	NP_075562.2
ZNF649-AS1	NR_110733.1 linkuse as main transcript	n.102+3165C>T		intron_variant, non_coding_transcript_variant
ZNF649	XM_047439238.1 linkuse as main transcript	c.833G>A	p.Arg278Lys	missense_variant	5/5		XP_047295194.1
ZNF649	XM_047439239.1 linkuse as main transcript	c.410G>A	p.Arg137Lys	missense_variant	3/3		XP_047295195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF649	ENST00000354957.8 linkuse as main transcript	c.845G>A	p.Arg282Lys	missense_variant	5/5	1	NM_023074.4	ENSP00000347043	P1
ZNF649	ENST00000600738.5 linkuse as main transcript	c.761G>A	p.Arg254Lys	missense_variant	6/6	1		ENSP00000468983
ZNF649-AS1	ENST00000600329.1 linkuse as main transcript	n.102+3165C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000656

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

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 05, 2022

The c.845G>A (p.R282K) alteration is located in exon 5 (coding exon 4) of the ZNF649 gene. This alteration results from a G to A substitution at nucleotide position 845, causing the arginine (R) at amino acid position 282 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

0.32

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.032

DANN

Benign

0.77

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.21

T;T

M_CAP

Benign

0.00054

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.81

N;.

REVEL

Benign

0.020

Sift

Benign

0.069

T;.

Sift4G

Benign

0.22

T;T

Polyphen

0.0010

B;.

Vest4

0.047

MutPred

0.61

Gain of methylation at R282 (P = 0.0076);.;

MVP

0.46

MPC

0.22

ClinPred

0.054

GERP RS

-5.0

Varity_R

0.059

gMVP

0.049

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over