Variant 17-49298627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145365.3(ZNF652):c.1607G>A(p.Ser536Asn) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

ZNF652
NM_001145365.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697

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:

ZNF652 (HGNC:):

ZNF652 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04134327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF652	NM_001145365.3 linkuse as main transcript	c.1607G>A	p.Ser536Asn	missense_variant	6/6	ENST00000430262.3	NP_001138837.1	Q9Y2D9A8K9F2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF652	ENST00000430262.3 linkuse as main transcript	c.1607G>A	p.Ser536Asn	missense_variant	6/6	1	NM_001145365.3	ENSP00000416305.2	Q9Y2D9
ZNF652	ENST00000362063.6 linkuse as main transcript	c.1607G>A	p.Ser536Asn	missense_variant	6/6	1		ENSP00000354686.2	Q9Y2D9
ZNF652	ENST00000508237.5 linkuse as main transcript	n.1067G>A		non_coding_transcript_exon_variant	7/8	2		ENSP00000424848.1	D6RF85
FLJ40194	ENST00000655089.1 linkuse as main transcript	n.863+8131C>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249006

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 08, 2024

The c.1607G>A (p.S536N) alteration is located in exon 6 (coding exon 5) of the ZNF652 gene. This alteration results from a G to A substitution at nucleotide position 1607, causing the serine (S) at amino acid position 536 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.1

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.17

Sift

Benign

0.37

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0

B;B

Vest4

0.051

MutPred

0.29

Loss of glycosylation at S536 (P = 5e-04);Loss of glycosylation at S536 (P = 5e-04);

MVP

0.068

MPC

0.36

ClinPred

0.14

GERP RS

2.3

Varity_R

0.042

gMVP

0.099

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