rs3745651

Variant names:

• chr19-12581187-G-T
• rs3745651
• NM_020714.3:c.888C>A
• ZNF490 p.His296Gln

Your query was ambiguous. Multiple possible variants found:

• chr19-12581187-G-T
• chr19-12581187-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020714.3(ZNF490):​c.888C>A​(p.His296Gln) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF490 NM_020714.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 34 publications found

Genes affected

ZNF490 (HGNC:23705): (zinc finger protein 490) 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]

ENSG00000269693 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020714.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF490	NM_020714.3	MANE Select	c.888C>A	p.His296Gln	missense	Exon 5 of 5	NP_065765.1	Q9ULM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF490	ENST00000311437.11	TSL:1 MANE Select	c.888C>A	p.His296Gln	missense	Exon 5 of 5	ENSP00000311521.6	Q9ULM2
	ZNF490	ENST00000944721.1		c.885C>A	p.His295Gln	missense	Exon 5 of 5	ENSP00000614780.1
	ENSG00000269693	ENST00000593682.1	TSL:1	n.-214C>A		upstream_gene	N/A	ENSP00000473043.1	M0R378

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 54994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	10
DANN	Benign	0.84
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		-0.71
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.63
gMVP		0.065
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3745651;

hg19: chr19-12692001;