chr19-58433706-A-G

Variant names:

• chr19-58433706-A-G
• NM_003433.4:c.1738T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003433.4(ZNF132):​c.1738T>C​(p.Phe580Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 8.15

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF132	NM_003433.4	c.1738T>C	p.Phe580Leu	missense_variant	Exon 3 of 3	ENST00000254166.4	NP_003424.3
ZNF132	XM_047439361.1	c.1699T>C	p.Phe567Leu	missense_variant	Exon 3 of 3		XP_047295317.1
ZNF324B	XM_047438807.1	c.-5-5735A>G		intron_variant	Intron 1 of 4		XP_047294763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF132	ENST00000254166.4	c.1738T>C	p.Phe580Leu	missense_variant	Exon 3 of 3	1	NM_003433.4	ENSP00000254166.2
ZNF132	ENST00000599148.1	n.1879T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ZNF132	ENST00000703732.1	n.2204T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1738T>C (p.F580L) 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 1738, causing the phenylalanine (F) at amino acid position 580 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		8.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.4	D;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0040	D;.
Polyphen		1.0	D;.
Vest4		0.60
MutPred		0.74		Gain of helix (P = 0.132);.;
MVP		0.86
MPC		0.096
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.62
gMVP		0.051
Mutation Taster		=82/18	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

Publications

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Other links and lift over

hg19: chr19-58945073;