rs150047025

Variant names:

• chr19-12580520-C-A
• rs150047025
• NM_020714.3:c.1555G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-12580520-C-A
• chr19-12580520-C-T
• chr19-12580520-C-G

Variant summary

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

The NM_020714.3(ZNF490):​c.1555G>T​(p.Val519Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,609,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V519M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: ZNF490 NM_020714.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.18
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06260142).

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.1555G>T	p.Val519Leu	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.1555G>T	p.Val519Leu	missense	Exon 5 of 5	ENSP00000311521.6	Q9ULM2
	ENSG00000269693	ENST00000593682.1	TSL:1	n.454G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000473043.1	M0R378
	ZNF490	ENST00000944721.1		c.1552G>T	p.Val518Leu	missense	Exon 5 of 5	ENSP00000614780.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 247418 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000357

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000508 AC: 74 AN: 1456958 Hom.: 0 Cov.: 38 AF XY: 0.0000400 AC XY: 29 AN XY: 724556

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 43938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25698

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85612

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000631 AC: 70 AN: 1109562

Other (OTH) AF: 0.0000499 AC: 3 AN: 60168

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.0000483 AC: 2 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000192 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.24
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.034
DANN	Benign	0.67
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-4.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.0040
Sift	Benign	0.65	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.042
MutPred		0.22		Loss of MoRF binding (P = 0.0847)
MVP		0.088
MPC		0.26
ClinPred		0.028	T
GERP RS		-0.31
Varity_R		0.036
gMVP		0.024
Mutation Taster		=99/1	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

dbSNP: rs150047025; hg19: chr19-12691334;