NM_003433.4:c.1854G>A

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

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