19-58434198-A-G

Position:

• chr19-58434198-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003433.4(ZNF132):​c.1246T>C​(p.Ser416Pro) 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. 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: -0.201

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3335884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF132	NM_003433.4	c.1246T>C	p.Ser416Pro	missense_variant	3/3	ENST00000254166.4	NP_003424.3
ZNF132	XM_047439361.1	c.1207T>C	p.Ser403Pro	missense_variant	3/3		XP_047295317.1
ZNF324B	XM_047438807.1	c.-5-5243A>G		intron_variant			XP_047294763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF132	ENST00000254166.4	c.1246T>C	p.Ser416Pro	missense_variant	3/3	1	NM_003433.4	ENSP00000254166.2
ZNF132	ENST00000599148.1	n.1387T>C		non_coding_transcript_exon_variant	1/1	6
ZNF132	ENST00000703732.1	n.1712T>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

May 05, 2023

The c.1246T>C (p.S416P) 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 1246, causing the serine (S) at amino acid position 416 to be replaced by a proline (P). 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	0.95
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.11
Sift	Benign	0.11	T;.
Sift4G	Benign	0.15	T;.
Polyphen		0.28	B;.
Vest4		0.38
MutPred		0.72		Loss of MoRF binding (P = 0.0594);.;
MVP		0.18
MPC		0.095
ClinPred		0.88	D
GERP RS		2.4
Varity_R		0.61
gMVP		0.26

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: chr19-58945565;