20-46501314-C-A

Position:

• chr20-46501314-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.2025G>T​(p.Gln675His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF334 NM_001353824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.302

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=0.109601974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF334	NM_001353824.2	c.2025G>T	p.Gln675His	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.2025G>T	p.Gln675His	missense_variant	5/5		NM_001353824.2	ENSP00000510334.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 08, 2022

The c.2025G>T (p.Q675H) 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 2025, causing the glutamine (Q) at amino acid position 675 to be replaced by a histidine (H). 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	0.38
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	.;T;.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.11	T;T;T;T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.5	.;D;D;.;.
REVEL	Benign	0.075
Sift	Benign	0.043	.;D;D;.;.
Sift4G	Uncertain	0.036	D;D;D;D;D
Polyphen		0.50, 0.65	.;P;.;P;.
Vest4		0.088
MutPred		0.51		.;.;.;Loss of MoRF binding (P = 0.0865);.;
MVP		0.34
MPC		0.036
ClinPred		0.30	T
GERP RS		3.2
Varity_R		0.28
gMVP		0.038

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: chr20-45129953;