19-12319135-C-G

Variant names:

• chr19-12319135-C-G
• rs373409197
• NM_145276.3:c.890G>C

Variant summary

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

The NM_145276.3(ZNF563):​c.890G>C​(p.Arg297Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R297Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF563 NM_145276.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 0 publications found

Genes affected

ZNF563 (HGNC:30498): (zinc finger protein 563) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145276.3. 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
	ZNF563	NM_145276.3	MANE Select	c.890G>C	p.Arg297Pro	missense	Exon 4 of 4	NP_660319.1	Q8TA94-1
	ZNF563	NM_001363608.1		c.*82G>C		3_prime_UTR	Exon 5 of 5	NP_001350537.1	A0A0C4DGQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF563	ENST00000293725.10	TSL:1 MANE Select	c.890G>C	p.Arg297Pro	missense	Exon 4 of 4	ENSP00000293725.5	Q8TA94-1
	ZNF563	ENST00000873252.1		c.368G>C	p.Arg123Pro	missense	Exon 4 of 4	ENSP00000543311.1
	ZNF563	ENST00000595977.5	TSL:5	c.*82G>C		downstream_gene	N/A	ENSP00000469879.1	A0A0C4DGQ9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0011	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-3.3
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.057
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.041	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.58		Loss of MoRF binding (P = 0.0084)
MVP		0.26
MPC		0.55
ClinPred		0.97	D
GERP RS		-1.4
Varity_R		0.53
gMVP		0.14
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: rs373409197; hg19: chr19-12429949;