Variant 19-11483702-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138783.4(ZNF653):c.1828C>T(p.Pro610Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ZNF653
NM_138783.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

Variant links:

Genes affected

ZNF653 (HGNC:25196): (zinc finger protein 653) Enables AF-2 domain binding activity and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of nucleic acid-templated transcription. Predicted to be located in extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF653 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF653	NM_138783.4 linkuse as main transcript	c.1828C>T	p.Pro610Ser	missense_variant	9/9	ENST00000293771.10	NP_620138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF653	ENST00000293771.10 linkuse as main transcript	c.1828C>T	p.Pro610Ser	missense_variant	9/9	1	NM_138783.4	ENSP00000293771	P1
ZNF653	ENST00000590296.5 linkuse as main transcript	c.401C>T	p.Pro134Leu	missense_variant	4/4	3		ENSP00000465166
ZNF653	ENST00000589051.1 linkuse as main transcript	c.*102C>T		3_prime_UTR_variant	3/3	5		ENSP00000465955
ZNF653	ENST00000590548.5 linkuse as main transcript	n.1996C>T		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250376

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135634

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460836

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 22, 2022

The c.1828C>T (p.P610S) alteration is located in exon 9 (coding exon 9) of the ZNF653 gene. This alteration results from a C to T substitution at nucleotide position 1828, causing the proline (P) at amino acid position 610 to be replaced by a serine (S). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.74

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-7.3

REVEL

Benign

0.29

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.63

MutPred

0.29

Loss of glycosylation at P610 (P = 0.0314);

MVP

0.53

MPC

1.8

ClinPred

0.98

GERP RS

3.9

Varity_R

0.60

gMVP

0.46

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