NM_018260.3:c.55C>G

Variant names:

• chr19-52575934-C-G
• NM_018260.3:c.55C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018260.3(ZNF701):​c.55C>G​(p.Gln19Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: ZNF701 NM_018260.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50
• Publications: 0 publications found

Genes affected

ZNF701 (HGNC:25597): (zinc finger protein 701) 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]

ENSG00000268886 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12411693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF701	NM_018260.3	c.55C>G	p.Gln19Glu	missense_variant	Exon 3 of 4	ENST00000391785.8	NP_060730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF701	ENST00000391785.8	c.55C>G	p.Gln19Glu	missense_variant	Exon 3 of 4	1	NM_018260.3	ENSP00000375662.2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 26

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253C>G (p.Q85E) alteration is located in exon 4 (coding exon 3) of the ZNF701 gene. This alteration results from a C to G substitution at nucleotide position 253, causing the glutamine (Q) at amino acid position 85 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	Benign	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.7
DANN	Benign	0.95
DEOGEN2	Benign	0.0052	.;.;T;.;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.043	T;T;.;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	.;M;.;.;.
PhyloP100		-2.5
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	.;N;N;.;N
REVEL	Benign	0.11
Sift	Benign	0.052	.;T;D;.;D
Sift4G	Benign	0.17	T;T;T;T;T
Vest4		0.20, 0.20
MutPred		0.57		.;.;Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.14
MPC		3.5
ClinPred		0.16	T
GERP RS		0.95
Varity_R		0.084
gMVP		0.029
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr19-53079187;