Genetic Variant ZNF132:p.Arg667Ile (chr19-58433444-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003433.4(ZNF132):c.2000G>T(p.Arg667Ile) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R667T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF132
NM_003433.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Variant links:

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]

ZNF132 links:

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]

ZNF324B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20571047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF132	NM_003433.4 link	c.2000G>T	p.Arg667Ile	missense_variant	Exon 3 of 3	ENST00000254166.4	NP_003424.3	P52740-1B3KQ54
ZNF132	XM_047439361.1 link	c.1961G>T	p.Arg654Ile	missense_variant	Exon 3 of 3		XP_047295317.1
ZNF324B	XM_047438807.1 link	c.-5-5997C>A		intron_variant	Intron 1 of 4		XP_047294763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF132	ENST00000254166.4 link	c.2000G>T	p.Arg667Ile	missense_variant	Exon 3 of 3	1	NM_003433.4	ENSP00000254166.2	P52740-1
ZNF132	ENST00000599148.1 link	n.2141G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ZNF132	ENST00000703732.1 link	n.2466G>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.56

N;.

PhyloP100

-1.8

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.5

N;.

REVEL

Benign

0.082

Sift

Benign

0.064

T;.

Sift4G

Benign

0.23

T;.

Polyphen

0.99

D;.

Vest4

0.36

MutPred

0.54

Loss of disorder (P = 0.0087);.;

MVP

0.14

MPC

0.094

ClinPred

0.70

GERP RS

3.0

Varity_R

0.12

gMVP

0.055

Mutation Taster

=96/4

polymorphism

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over