chr19-56423115-G-T

Position:

• chr19-56423115-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152478.3(ZNF583):​c.457G>T​(p.Val153Phe) 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. 14/21 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)
• Consequence: ZNF583 NM_152478.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0742006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF583	NM_152478.3	c.457G>T	p.Val153Phe	missense_variant	5/5	ENST00000333201.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF583	ENST00000333201.13	c.457G>T	p.Val153Phe	missense_variant	5/5	2	NM_152478.3	P1
ZNF583	ENST00000291598.11	c.457G>T	p.Val153Phe	missense_variant	5/5	3		P1
ZNF583	ENST00000585612.1			upstream_gene_variant		1
ZNF583	ENST00000391778.3			downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00029	N
LIST_S2	Benign	0.050	T;.
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.070	N;N
REVEL	Benign	0.015
Sift	Benign	0.12	T;T
Sift4G	Benign	0.071	T;T
Polyphen		0.0040	B;B
Vest4		0.18
MutPred		0.40		Loss of ubiquitination at K156 (P = 0.1601);Loss of ubiquitination at K156 (P = 0.1601);
MVP		0.23
MPC		0.68
ClinPred		0.079	T
GERP RS		-0.55
Varity_R		0.033
gMVP		0.28

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

Other links and lift over

dbSNP: rs2042443734; hg19: chr19-56934484;