rs865909396

Variant names:

• chr6-87215999-C-G
• rs865909396
• NM_015021.3:c.265C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-87215999-C-G
• chr6-87215999-C-T

Variant summary

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

The NM_015021.3(ZNF292):​c.265C>G​(p.Arg89Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF292 NM_015021.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 4 publications found

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]

ZNF292 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• intellectual developmental disorder, autosomal dominant 64

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

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
ZNF292	NM_015021.3	c.265C>G	p.Arg89Gly	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.265C>G	p.Arg89Gly	missense_variant	Exon 2 of 8	1	NM_015021.3	ENSP00000358590.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	0.0061	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		2.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.43	T;T
Polyphen		0.93	P;.
Vest4		0.72
MutPred		0.40		Gain of ubiquitination at K87 (P = 0.0497);Gain of ubiquitination at K87 (P = 0.0497);
MVP		0.15
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.51
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs865909396; hg19: chr6-87925717; COSMIC: COSV60538268;