NM_015021.3:c.189G>C

Variant names:

• chr6-87215923-G-C
• NM_015021.3:c.189G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015021.3(ZNF292):​c.189G>C​(p.Glu63Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF292 NM_015021.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.312

Genes affected

ZNF292 (HGNC:18410): (zinc finger protein 292) This gene encodes a growth hormone-dependent, zinc finger transcription factor that functions as a tumor suppressor. Naturally occurring mutations in this gene are associated with gastric cancer, colorectal cancer, and chronic lymphocytic leukemia. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1846757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF292	NM_015021.3	c.189G>C	p.Glu63Asp	missense_variant	Exon 2 of 8	ENST00000369577.8	NP_055836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF292	ENST00000369577.8	c.189G>C	p.Glu63Asp	missense_variant	Exon 2 of 8	1	NM_015021.3	ENSP00000358590.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446872 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 719912

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF292: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.072	T;T
Eigen	Benign	0.0085
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.065
Sift	Benign	0.32	T;T
Sift4G	Benign	0.98	T;T
Polyphen		0.54	P;.
Vest4		0.44
MutPred		0.20		Loss of ubiquitination at K64 (P = 0.0683);Loss of ubiquitination at K64 (P = 0.0683);
MVP		0.36
ClinPred		0.14	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.053
gMVP		0.27

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: chr6-87925641;