19-44157700-C-T

Position:

• chr19-44157700-C-T

Variant summary

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

The NM_006630.3(ZNF234):​c.1684C>T​(p.His562Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF234 NM_006630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF234	NM_006630.3	c.1684C>T	p.His562Tyr	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.1684C>T	p.His562Tyr	missense_variant	6/6	1	NM_006630.3	ENSP00000400878	P1
ZNF234	ENST00000592437.5	c.1684C>T	p.His562Tyr	missense_variant	6/6	1		ENSP00000465011	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 23, 2024

The c.1684C>T (p.H562Y) alteration is located in exon 6 (coding exon 4) of the ZNF234 gene. This alteration results from a C to T substitution at nucleotide position 1684, causing the histidine (H) at amino acid position 562 to be replaced by a tyrosine (Y). 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	0.87
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	0.035
Eigen_PC	Benign	0.010
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.4	M;M
MutationTaster	Benign	0.83	N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.6	.;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	.;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.10	B;B
Vest4		0.41
MutPred		0.72		Gain of phosphorylation at H562 (P = 0.0274);Gain of phosphorylation at H562 (P = 0.0274);
MVP		0.86
MPC		0.21
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.088
gMVP		0.062

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

LitVar

Other links and lift over

dbSNP: rs1239362699; hg19: chr19-44661853;