chr19-52574123-G-C

Position:

• chr19-52574123-G-C

Variant summary

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

The NM_001172655.1(ZNF701):​c.174G>C​(p.Arg58Ser) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF701 NM_001172655.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.920

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]

ZNF701 (HGNC:):

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=0.10569951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF701	NM_018260.3	c.-25G>C		5_prime_UTR_variant	2/4	ENST00000391785.8	NP_060730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF701	ENST00000391785	c.-25G>C		5_prime_UTR_variant	2/4	1	NM_018260.3	ENSP00000375662.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 07, 2024

The c.174G>C (p.R58S) alteration is located in exon 3 (coding exon 2) of the ZNF701 gene. This alteration results from a G to C substitution at nucleotide position 174, causing the arginine (R) at amino acid position 58 to be replaced by a serine (S). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0024	.;T;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.16	T;.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.52	.;N;.;N
REVEL	Benign	0.031
Sift	Benign	0.069	.;T;.;T
Sift4G	Benign	0.20	T;T;T;T
Vest4		0.22
MutPred		0.37		.;Gain of phosphorylation at R58 (P = 0.0023);Gain of phosphorylation at R58 (P = 0.0023);Gain of phosphorylation at R58 (P = 0.0023);
MVP		0.22
MPC		0.25
ClinPred		0.17	T
GERP RS		0.46
Varity_R		0.11
gMVP		0.082

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: chr19-53077376;