19-12581065-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

Verdict is Likely_benign. Variant got -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 id is 3476466.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF490	NM_020714.3	c.1010G>A	p.Arg337Lys	missense_variant	Exon 5 of 5	ENST00000311437.11	NP_065765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF490	ENST00000311437.11	c.1010G>A	p.Arg337Lys	missense_variant	Exon 5 of 5	1	NM_020714.3	ENSP00000311521.6
ENSG00000269693	ENST00000593682.1	n.-92G>A		upstream_gene_variant		1		ENSP00000473043.1
ZNF490	ENST00000414906.5	n.*932G>A		downstream_gene_variant		3		ENSP00000402719.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 29, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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
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

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: chr19-12691879;