19-44156275-G-A

Position:

• chr19-44156275-G-A

Variant summary

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

The NM_006630.3(ZNF234):​c.259G>A​(p.Glu87Lys) 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: ZNF234 NM_006630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

Genes affected

ZNF234 (HGNC:13027): (zinc finger protein 234) 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=0.08658871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF234	NM_006630.3	c.259G>A	p.Glu87Lys	missense_variant	6/6	ENST00000426739.7	NP_006621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF234	ENST00000426739.7	c.259G>A	p.Glu87Lys	missense_variant	6/6	1	NM_006630.3	ENSP00000400878	P1
ZNF234	ENST00000592437.5	c.259G>A	p.Glu87Lys	missense_variant	6/6	1		ENSP00000465011	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 30, 2022

The c.259G>A (p.E87K) alteration is located in exon 6 (coding exon 4) of the ZNF234 gene. This alteration results from a G to A substitution at nucleotide position 259, causing the glutamic acid (E) at amino acid position 87 to be replaced by a lysine (K). 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	Benign	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0071	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.93	L;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.86	.;N
REVEL	Benign	0.061
Sift	Benign	0.29	.;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.54		Gain of methylation at E87 (P = 0.0062);Gain of methylation at E87 (P = 0.0062);
MVP		0.23
MPC		0.11
ClinPred		0.12	T
GERP RS		0.58
Varity_R		0.032
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs959451284; hg19: chr19-44660428;