Variant 19-56423746-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_152478.3(ZNF583):c.1088A>C(p.His363Pro) 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. 13/21 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: 0.00037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF583
NM_152478.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.246

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36703682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF583	NM_152478.3 link	c.1088A>C	p.His363Pro	missense_variant	5/5	ENST00000333201.13	NP_689691.2	Q96ND8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF583	ENST00000333201.13 link	c.1088A>C	p.His363Pro	missense_variant	5/5	2	NM_152478.3	ENSP00000388502.2	Q96ND8
ZNF583	ENST00000585612.1 link	n.597A>C		non_coding_transcript_exon_variant	1/2	1
ZNF583	ENST00000291598.11 link	c.1088A>C	p.His363Pro	missense_variant	5/5	3		ENSP00000291598.7	Q96ND8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000366

AC:

534

AN:

1458502

Hom.:

Cov.:

AF XY:

0.000345

AC XY:

250

AN XY:

725678

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000445

Gnomad4 OTH exome

AF:

0.000265

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

Sep 03, 2024

The c.1088A>C (p.H363P) alteration is located in exon 5 (coding exon 4) of the ZNF583 gene. This alteration results from a A to C substitution at nucleotide position 1088, causing the histidine (H) at amino acid position 363 to be replaced by a proline (P). 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

0.85

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.000070

LIST_S2

Benign

0.27

T;.

M_CAP

Benign

0.0086

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.10

Sift

Benign

0.20

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.96

D;D

Vest4

0.32

MutPred

0.67

Loss of catalytic residue at H363 (P = 0.0585);Loss of catalytic residue at H363 (P = 0.0585);

MVP

0.42

MPC

1.8

ClinPred

0.43

GERP RS

2.2

Varity_R

0.27

gMVP

0.52

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