19-22088237-C-T

Position:

• chr19-22088237-C-T

Variant summary

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

The NM_033468.4(ZNF257):​c.487C>T​(p.His163Tyr) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF257 NM_033468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

Genes affected

ZNF257 (HGNC:13498): (zinc finger protein 257) 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, DNA-templated. Predicted to be located 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=0.14079407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF257	NM_033468.4	c.487C>T	p.His163Tyr	missense_variant	4/4	ENST00000594947.6	NP_258429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF257	ENST00000594947.6	c.487C>T	p.His163Tyr	missense_variant	4/4	4	NM_033468.4	ENSP00000470209.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Nov 29, 2021

The c.487C>T (p.H163Y) alteration is located in exon 4 (coding exon 4) of the ZNF257 gene. This alteration results from a C to T substitution at nucleotide position 487, causing the histidine (H) at amino acid position 163 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	Benign	0.083
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.2
DANN	Benign	0.74
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.098	T;T
Polyphen		0.36	.;B
Vest4		0.19
MutPred		0.39		.;Loss of disorder (P = 0.0753);
MVP		0.58
MPC		0.010
ClinPred		0.094	T
GERP RS		-1.0
Varity_R		0.12
gMVP		0.028

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: chr19-22271039;