19-44157539-G-A

Position:

• chr19-44157539-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000426739.7(ZNF234):​c.1523G>A​(p.Gly508Glu) 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: 32)
• Consequence: ZNF234 ENST00000426739.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3525867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF234	NM_006630.3	c.1523G>A	p.Gly508Glu	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.1523G>A	p.Gly508Glu	missense_variant	6/6	1	NM_006630.3	ENSP00000400878.1
ZNF234	ENST00000592437.5	c.1523G>A	p.Gly508Glu	missense_variant	6/6	1		ENSP00000465011.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

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

Apr 20, 2024

The c.1523G>A (p.G508E) 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 1523, causing the glycine (G) at amino acid position 508 to be replaced by a glutamic acid (E). 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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.56	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-7.7	.;D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;D
Vest4		0.19
MutPred		0.63		Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP		0.76
MPC		0.59
ClinPred		1.0	D
GERP RS		3.0
Varity_R		0.15
gMVP		0.022

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-44661692;