19-58433895-A-G

Position:

• chr19-58433895-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003433.4(ZNF132):​c.1549T>C​(p.Cys517Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF132 NM_003433.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

Genes affected

ZNF132 (HGNC:12916): (zinc finger protein 132) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF324B (HGNC:33107): (zinc finger protein 324B) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF132	NM_003433.4	c.1549T>C	p.Cys517Arg	missense_variant	3/3	ENST00000254166.4	NP_003424.3
ZNF132	XM_047439361.1	c.1510T>C	p.Cys504Arg	missense_variant	3/3		XP_047295317.1
ZNF324B	XM_047438807.1	c.-5-5546A>G		intron_variant			XP_047294763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF132	ENST00000254166.4	c.1549T>C	p.Cys517Arg	missense_variant	3/3	1	NM_003433.4	ENSP00000254166.2
ZNF132	ENST00000599148.1	n.1690T>C		non_coding_transcript_exon_variant	1/1	6
ZNF132	ENST00000703732.1	n.2015T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 23, 2023

The c.1549T>C (p.C517R) alteration is located in exon 3 (coding exon 3) of the ZNF132 gene. This alteration results from a T to C substitution at nucleotide position 1549, causing the cysteine (C) at amino acid position 517 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.66		Gain of MoRF binding (P = 0.0073);
MVP		0.89
MPC		0.098
ClinPred		1.0	D
GERP RS		2.5
Varity_R		0.78
gMVP		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58945262;