19-12349856-A-G

Variant names:

• chr19-12349856-A-G
• NM_030824.3:c.1729T>C

Variant summary

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

The NM_030824.3(ZNF442):​c.1729T>C​(p.Cys577Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF442 NM_030824.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.22
• Publications: 0 publications found

Genes affected

ZNF442 (HGNC:20877): (zinc finger protein 442) 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_030824.3. 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
	ZNF442	NM_030824.3	MANE Select	c.1729T>C	p.Cys577Arg	missense	Exon 6 of 6	NP_110451.1	Q9H7R0-1
	ZNF442	NM_001363774.2		c.1522T>C	p.Cys508Arg	missense	Exon 3 of 3	NP_001350703.1	Q9H7R0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF442	ENST00000242804.9	TSL:2 MANE Select	c.1729T>C	p.Cys577Arg	missense	Exon 6 of 6	ENSP00000242804.4	Q9H7R0-1
	ZNF442	ENST00000545749.2	TSL:5	c.1729T>C	p.Cys577Arg	missense	Exon 4 of 4	ENSP00000440162.2	Q9H7R0-1
	ZNF442	ENST00000438182.5	TSL:2	c.1522T>C	p.Cys508Arg	missense	Exon 3 of 3	ENSP00000388634.1	Q9H7R0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

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: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.035	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		5.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-9.8	D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.72		Gain of MoRF binding (P = 0.0086)
MVP		0.85
MPC		0.49
ClinPred		0.99	D
GERP RS		0.79
Varity_R		0.74
gMVP		0.054
Mutation Taster		=98/2	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: chr19-12460670;