19-44157445-A-G

Position:

• chr19-44157445-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006630.3(ZNF234):​c.1429A>G​(p.Ile477Val) 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. 15/21 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: 0.0400

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059820592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF234	NM_006630.3	c.1429A>G	p.Ile477Val	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.1429A>G	p.Ile477Val	missense_variant	6/6	1	NM_006630.3	ENSP00000400878	P1
ZNF234	ENST00000592437.5	c.1429A>G	p.Ile477Val	missense_variant	6/6	1		ENSP00000465011	P1

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

Aug 02, 2021

The c.1429A>G (p.I477V) alteration is located in exon 6 (coding exon 4) of the ZNF234 gene. This alteration results from a A to G substitution at nucleotide position 1429, causing the isoleucine (I) at amino acid position 477 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.2
DANN	Benign	0.50
DEOGEN2	Benign	0.0017	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.0	.;N
REVEL	Benign	0.021
Sift	Benign	1.0	.;T
Sift4G	Benign	0.38	T;T
Polyphen		0.15	B;B
Vest4		0.084
MutPred		0.41		Gain of ubiquitination at K482 (P = 0.1062);Gain of ubiquitination at K482 (P = 0.1062);
MVP		0.20
MPC		0.11
ClinPred		0.072	T
GERP RS		-0.51
Varity_R		0.016
gMVP		0.0099

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: chr19-44661598;