chr19-52431487-C-A

Position:

• chr19-52431487-C-A

Variant summary

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

The NM_001351679.2(ZNF534):​c.56C>A​(p.Ser19*) variant causes a stop gained, splice region 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. S19S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF534 NM_001351679.2 stop_gained, splice_region
• Scores: Splicing: ADA: 0.0002783
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.494

Genes affected

ZNF534 (HGNC:26337): (zinc finger protein 534) 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 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
ZNF534	NM_001143938.3	c.13C>A	p.Gln5Lys	missense_variant, splice_region_variant	2/5	ENST00000433050.6	NP_001137410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF534	ENST00000433050.6	c.13C>A	p.Gln5Lys	missense_variant, splice_region_variant	2/5	1	NM_001143938.3	ENSP00000391358.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.0091	.;.;T;T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.59	.;T;T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	.;M;M;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.7	D;N;N;D;.
REVEL	Benign	0.023
Sift	Benign	0.037	D;D;D;D;.
Sift4G	Uncertain	0.047	D;D;T;T;D
Polyphen		0.11	B;B;B;P;B
Vest4		0.22
MutPred		0.37		Gain of ubiquitination at S5 (P = 0.0185);Gain of ubiquitination at S5 (P = 0.0185);Gain of ubiquitination at S5 (P = 0.0185);Gain of ubiquitination at S5 (P = 0.0185);Gain of ubiquitination at S5 (P = 0.0185);
MVP		0.13
MPC		0.18
ClinPred		0.34	T
GERP RS		1.2
Varity_R		0.18
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.022
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: rs193921143; hg19: chr19-52934740; COSMIC: COSV56514712;