Genetic Variant NM_001145365.3:c.1703C>T (chr17-49298531-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145365.3(ZNF652):c.1703C>T(p.Pro568Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF652
NM_001145365.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2085062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF652	NM_001145365.3 link	c.1703C>T	p.Pro568Leu	missense_variant	Exon 6 of 6	ENST00000430262.3	NP_001138837.1	Q9Y2D9A8K9F2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF652	ENST00000430262.3 link	c.1703C>T	p.Pro568Leu	missense_variant	Exon 6 of 6	1	NM_001145365.3	ENSP00000416305.2	Q9Y2D9
ZNF652	ENST00000362063.6 link	c.1703C>T	p.Pro568Leu	missense_variant	Exon 6 of 6	1		ENSP00000354686.2	Q9Y2D9
ZNF652	ENST00000508237.5 link	n.1163C>T		non_coding_transcript_exon_variant	Exon 7 of 8	2		ENSP00000424848.1	D6RF85
FLJ40194	ENST00000655089.1 link	n.863+8035G>A		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460220

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5268

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111512

Other (OTH)

AF:

0.00

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1703C>T (p.P568L) alteration is located in exon 6 (coding exon 5) of the ZNF652 gene. This alteration results from a C to T substitution at nucleotide position 1703, causing the proline (P) at amino acid position 568 to be replaced by a leucine (L). 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

0.070

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

0.065

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.5

L;L

PhyloP100

7.6

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.057

T;T

Polyphen

0.18

B;B

Vest4

0.40

MutPred

0.31

Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);

MVP

0.28

MPC

1.1

ClinPred

0.97

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.14

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over