chr19-24126469-G-A

Position:

• chr19-24126469-G-A

Variant summary

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

The ENST00000357002.5(ZNF254):​c.469G>A​(p.Asp157Asn) 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: 33)
• Consequence: ZNF254 ENST00000357002.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.133

Genes affected

ZNF254 (HGNC:13047): (zinc finger protein 254) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See ZFP93 (MIM 604749) for additional information on zinc finger proteins.[supplied by OMIM, Jul 2002]

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=0.055099636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF254	NM_203282.4	c.469G>A	p.Asp157Asn	missense_variant	4/4	ENST00000357002.5	NP_975011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF254	ENST00000357002.5	c.469G>A	p.Asp157Asn	missense_variant	4/4	1	NM_203282.4	ENSP00000349494	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Sep 14, 2021

The c.469G>A (p.D157N) alteration is located in exon 4 (coding exon 4) of the ZNF254 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the aspartic acid (D) at amino acid position 157 to be replaced by an asparagine (N). 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	0.077
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.50
DANN	Benign	0.13
DEOGEN2	Benign	0.010	.;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.059	T;T;T;T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.055	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	.;.;.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.3	.;.;.;N
REVEL	Benign	0.017
Sift	Benign	0.43	.;.;.;T
Sift4G	Benign	0.97	T;T;T;T
Polyphen		0.032	.;.;.;B
Vest4		0.090
MutPred		0.33		.;.;.;Gain of MoRF binding (P = 0.0395);
MVP		0.10
MPC		0.0015
ClinPred		0.034	T
GERP RS		-0.052
Varity_R		0.038
gMVP		0.0023

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: chr19-24309271;