19-9653058-C-A

Variant names:

• chr19-9653058-C-A
• NM_001130031.2:c.1172G>T
• ZNF562 p.Arg391Ile

Variant summary

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

The NM_001130031.2(ZNF562):​c.1172G>T​(p.Arg391Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF562 NM_001130031.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• 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: 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=0.045042396).

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.1172G>T	p.Arg391Ile	missense	Exon 6 of 6	NP_001123503.1	Q6V9R5-1
	ZNF562	NM_001130032.2		c.1172G>T	p.Arg391Ile	missense	Exon 6 of 6	NP_001123504.1	Q6V9R5-1
	ZNF562	NM_001300885.2		c.1169G>T	p.Arg390Ile	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.1172G>T	p.Arg391Ile	missense	Exon 6 of 6	ENSP00000410734.1	Q6V9R5-1
	ZNF562	ENST00000901088.1		c.1172G>T	p.Arg391Ile	missense	Exon 6 of 6	ENSP00000571147.1
	ZNF562	ENST00000933425.1		c.1172G>T	p.Arg391Ile	missense	Exon 6 of 6	ENSP00000603484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.94
DANN	Benign	0.72
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.30	N
PhyloP100		-0.053
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.020
Sift	Benign	0.20	T
Sift4G	Uncertain	0.039	D
Varity_R		0.023
gMVP		0.095
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-9763734;