NM_020714.3:c.1010G>A

Variant names:

• chr19-12581065-C-T
• NM_020714.3:c.1010G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020714.3(ZNF490):​c.1010G>A​(p.Arg337Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF490 NM_020714.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77
• 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]

ENSG00000269693 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016471446).
• BP6: Variant 19-12581065-C-T is Benign according to our data. Variant chr19-12581065-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3476466.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1010G>A	p.Arg337Lys	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.1010G>A	p.Arg337Lys	missense	Exon 5 of 5	ENSP00000311521.6	Q9ULM2
	ZNF490	ENST00000944721.1		c.1007G>A	p.Arg336Lys	missense	Exon 5 of 5	ENSP00000614780.1
	ENSG00000269693	ENST00000593682.1	TSL:1	n.-92G>A		upstream_gene	N/A	ENSP00000473043.1	M0R378

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.81
DANN	Benign	0.39
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.00072	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.57	N
PhyloP100		-2.8
PrimateAI	Benign	0.22	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.038
MutPred		0.35		Gain of methylation at R337 (P = 0.0016)
MVP		0.14
MPC		0.27
ClinPred		0.039	T
GERP RS		-0.24
Varity_R		0.042
gMVP		0.020
Mutation Taster		=100/0	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: chr19-12691879;