chr19-21423123-A-G

Variant names:

• chr19-21423123-A-G
• rs903983069
• NM_001076678.3:c.464A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001076678.3(ZNF493):​c.464A>G​(p.Gln155Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q155P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF493 NM_001076678.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 0 publications found

Genes affected

ZNF493 (HGNC:23708): (zinc finger protein 493) Predicted to enable DNA-binding transcription activator 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]

ENSG00000269237 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11082086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF493	NM_001076678.3	c.464A>G	p.Gln155Arg	missense_variant	Exon 4 of 4	ENST00000392288.7	NP_001070146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF493	ENST00000392288.7	c.464A>G	p.Gln155Arg	missense_variant	Exon 4 of 4	1	NM_001076678.3	ENSP00000376110.2
ENSG00000269237	ENST00000600810.1	n.196+17267A>G		intron_variant	Intron 2 of 4	3		ENSP00000473166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.063	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.17	T;T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	.;M
PhyloP100		-0.23
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.027
Sift	Benign	0.089	T;T
Sift4G	Benign	0.066	T;T
Polyphen		0.99	D;B
Vest4		0.10
MutPred		0.32		.;Gain of MoRF binding (P = 0.0122);
MVP		0.31
MPC		0.056
ClinPred		0.26	T
GERP RS		-0.10
Varity_R		0.060
gMVP		0.0096
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

dbSNP: rs903983069; hg19: chr19-21605925;