19-12581315-C-A

Variant names:

• chr19-12581315-C-A
• rs1018756407
• NM_020714.3:c.760G>T

Variant summary

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

The NM_020714.3(ZNF490):​c.760G>T​(p.Glu254*) variant causes a stop gained 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF490 NM_020714.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.760G>T	p.Glu254*	stop_gained	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.760G>T	p.Glu254*	stop_gained	Exon 5 of 5	ENSP00000311521.6	Q9ULM2
	ZNF490	ENST00000944721.1		c.757G>T	p.Glu253*	stop_gained	Exon 5 of 5	ENSP00000614780.1
	ZNF490	ENST00000414906.5	TSL:3	n.*682G>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000402719.1	F8WDW6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.0016	N
PhyloP100		-0.98
Vest4		0.041
GERP RS		-2.0
Mutation Taster		=192/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs1018756407; hg19: chr19-12692129;