19-58433590-C-T

Variant names:

• chr19-58433590-C-T
• rs138163038
• NM_003433.4:c.1854G>A

Variant summary

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

The NM_003433.4(ZNF132):​c.1854G>A​(p.Trp618*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF132 NM_003433.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF132	NM_003433.4	c.1854G>A	p.Trp618*	stop_gained	Exon 3 of 3	ENST00000254166.4	NP_003424.3
ZNF132	XM_047439361.1	c.1815G>A	p.Trp605*	stop_gained	Exon 3 of 3		XP_047295317.1
ZNF324B	XM_047438807.1	c.-5-5851C>T		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.1854G>A	p.Trp618*	stop_gained	Exon 3 of 3	1	NM_003433.4	ENSP00000254166.2
ZNF132	ENST00000599148.1	n.1995G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ZNF132	ENST00000703732.1	n.2320G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.050	N
PhyloP100		0.61
Vest4		0.043
GERP RS		2.7
Mutation Taster		=96/104	disease causing

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

dbSNP: rs138163038; hg19: chr19-58944957; COSMIC: COSV108787893; COSMIC: COSV108787893;