chr20-46501510-C-A

Position:

• chr20-46501510-C-A

Variant summary

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

The NM_001353824.2(ZNF334):​c.1829G>T​(p.Cys610Phe) 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: ZNF334 NM_001353824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.39

Genes affected

ZNF334 (HGNC:15806): (zinc finger protein 334) This gene encodes a member of the C2H2 zinc finger family. The encoded protein contains a Krueppel-associated box, fourteen C2H2 zinc finger domains, and four C2H2-type/integrase DNA-binding domains. Decreased expression of this gene may be a marker for rheumatoid arthritis. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ZNF334 (HGNC:):

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=0.08505115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF334	NM_001353824.2	c.1829G>T	p.Cys610Phe	missense_variant	5/5	ENST00000692313.1	NP_001340753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF334	ENST00000692313.1	c.1829G>T	p.Cys610Phe	missense_variant	5/5		NM_001353824.2	ENSP00000510334.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.1829G>T (p.C610F) alteration is located in exon 5 (coding exon 4) of the ZNF334 gene. This alteration results from a G to T substitution at nucleotide position 1829, causing the cysteine (C) at amino acid position 610 to be replaced by a phenylalanine (F). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0048	.;T;.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.00062	N
LIST_S2	Benign	0.19	T;T;T;T;.
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.085	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.26	.;N;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	.;N;N;.;.
REVEL	Benign	0.057
Sift	Benign	0.087	.;T;T;.;.
Sift4G	Benign	0.58	T;T;T;T;T
Polyphen		0.94, 0.98	.;P;.;D;.
Vest4		0.10
MutPred		0.51		.;.;.;Loss of ubiquitination at K630 (P = 0.0537);.;
MVP		0.18
MPC		0.16
ClinPred		0.51	D
GERP RS		3.2
Varity_R		0.21
gMVP		0.026

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.

Other links and lift over

hg19: chr20-45130149;