Variant 17-49317538-A-G 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_001145365.3(ZNF652):c.188T>C(p.Val63Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF652
NM_001145365.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

ZNF652 (HGNC:29147): (zinc finger protein 652) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF652 links:

FLJ40194 (HGNC:):

FLJ40194 links:

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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=0.16076678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF652	NM_001145365.3 linkuse as main transcript	c.188T>C	p.Val63Ala	missense_variant	2/6	ENST00000430262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF652	ENST00000430262.3 linkuse as main transcript	c.188T>C	p.Val63Ala	missense_variant	2/6	1	NM_001145365.3	P1
ZNF652	ENST00000362063.6 linkuse as main transcript	c.188T>C	p.Val63Ala	missense_variant	2/6	1		P1
FLJ40194	ENST00000655089.1 linkuse as main transcript	n.864-53A>G		intron_variant, non_coding_transcript_variant
ZNF652	ENST00000508237.5 linkuse as main transcript	c.188T>C	p.Val63Ala	missense_variant, NMD_transcript_variant	3/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

May 27, 2022

The c.188T>C (p.V63A) alteration is located in exon 2 (coding exon 1) of the ZNF652 gene. This alteration results from a T to C substitution at nucleotide position 188, causing the valine (V) at amino acid position 63 to be replaced by an alanine (A). 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

0.19

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Benign

0.68

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.066

MetaRNN

Benign

0.16

T;T

MetaSVM

Uncertain

0.61

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.88

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.047

D;D

Polyphen

0.0

B;B

Vest4

0.24

MutPred

0.39

Loss of stability (P = 5e-04);Loss of stability (P = 5e-04);

MVP

0.26

MPC

0.46

ClinPred

0.57

GERP RS

4.5

Varity_R

0.075

gMVP

0.27

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