Variant chr19-56423650-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152478.3(ZNF583):c.992A>T(p.Lys331Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF583
NM_152478.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09

Variant links:

Genes affected

ZNF583 (HGNC:26427): (zinc finger protein 583) 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]

ZNF583 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
ZNF583	NM_152478.3 linkuse as main transcript	c.992A>T	p.Lys331Met	missense_variant	5/5	ENST00000333201.13	NP_689691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF583	ENST00000333201.13 linkuse as main transcript	c.992A>T	p.Lys331Met	missense_variant	5/5	2	NM_152478.3	ENSP00000388502	P1
ZNF583	ENST00000585612.1 linkuse as main transcript	n.501A>T		non_coding_transcript_exon_variant	1/2	1
ZNF583	ENST00000291598.11 linkuse as main transcript	c.992A>T	p.Lys331Met	missense_variant	5/5	3		ENSP00000291598	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

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

Jan 18, 2022

The c.992A>T (p.K331M) alteration is located in exon 5 (coding exon 4) of the ZNF583 gene. This alteration results from a A to T substitution at nucleotide position 992, causing the lysine (K) at amino acid position 331 to be replaced by a methionine (M). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.57

T;.

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.39

MutPred

0.51

Loss of methylation at K331 (P = 0.0069);Loss of methylation at K331 (P = 0.0069);

MVP

0.69

MPC

1.7

ClinPred

0.99

GERP RS

4.3

Varity_R

0.66

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