19-52431487-C-A

Variant names:

• chr19-52431487-C-A
• rs193921143
• NM_001143938.3:c.13C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143938.3(ZNF534):​c.13C>A​(p.Gln5Lys) variant causes a missense, 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. 16/24 in silico tools predict 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).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF534 NM_001143938.3 missense, splice_region
• Scores: Splicing: ADA: 0.0002783
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.494
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118870944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF534	NM_001143938.3	c.13C>A	p.Gln5Lys	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000433050.6	NP_001137410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF534	ENST00000433050.6	c.13C>A	p.Gln5Lys	missense_variant, splice_region_variant	Exon 2 of 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

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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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;.;.
PhyloP100		0.49
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
PromoterAI		0.058	Neutral
Varity_R		0.18
gMVP		0.16
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs193921143; hg19: chr19-52934740; COSMIC: COSV56514712;