19-9653483-C-A

Variant names:

• chr19-9653483-C-A
• NM_001130031.2:c.747G>T

Variant summary

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

The NM_001130031.2(ZNF562):​c.747G>T​(p.Gln249His) 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. 15/22 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. Q249R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF562 NM_001130031.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.73
• Publications: 0 publications found

Genes affected

ZNF562 (HGNC:25950): (zinc finger protein 562) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF561-AS1 (HGNC:27613): (ZNF561 antisense RNA 1 (head to head))

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=0.10425207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130031.2. 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
	ZNF562	NM_001130031.2	MANE Select	c.747G>T	p.Gln249His	missense	Exon 6 of 6	NP_001123503.1	Q6V9R5-1
	ZNF562	NM_001130032.2		c.747G>T	p.Gln249His	missense	Exon 6 of 6	NP_001123504.1	Q6V9R5-1
	ZNF562	NM_001300885.2		c.744G>T	p.Gln248His	missense	Exon 6 of 6	NP_001287814.1	K7EIE6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF562	ENST00000453372.7	TSL:3 MANE Select	c.747G>T	p.Gln249His	missense	Exon 6 of 6	ENSP00000410734.1	Q6V9R5-1
	ZNF562	ENST00000901088.1		c.747G>T	p.Gln249His	missense	Exon 6 of 6	ENSP00000571147.1
	ZNF562	ENST00000933425.1		c.747G>T	p.Gln249His	missense	Exon 6 of 6	ENSP00000603484.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.27
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.014
DANN	Benign	0.88
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.0069	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-3.7
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.041
Sift	Benign	0.41	T
Sift4G	Benign	0.41	T
Polyphen		0.99	D
Vest4		0.055
MutPred		0.29		Loss of methylation at K248 (P = 0.0827)
MVP		0.14
ClinPred		0.18	T
GERP RS		-1.3
Varity_R		0.050
gMVP		0.073
Mutation Taster		=96/4	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: chr19-9764159;