rs9362399

Variant names:

• chr6-87164671-T-G
• rs9362399
• NM_015021.3:c.168+8912T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015021.3(ZNF292):​c.168+8912T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,120 control chromosomes in the GnomAD database, including 1,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1167 hom., cov: 32)
• Consequence: ZNF292 NM_015021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF292	NM_015021.3	c.168+8912T>G		intron_variant	Intron 1 of 7	ENST00000369577.8	NP_055836.1
ZNF292	NM_001351444.2	c.-398+8912T>G		intron_variant	Intron 1 of 8		NP_001338373.1
ZNF292	XM_047418459.1	c.-566+8912T>G		intron_variant	Intron 1 of 9		XP_047274415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF292	ENST00000369577.8	c.168+8912T>G		intron_variant	Intron 1 of 7	1	NM_015021.3	ENSP00000358590.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17653 AN: 152000 Hom.: 1164 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17681 AN: 152120 Hom.: 1167 Cov.: 32 AF XY: 0.116 AC XY: 8591 AN XY: 74374

African (AFR) AF: 0.174 AC: 7226 AN: 41474

American (AMR) AF: 0.0756 AC: 1156 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3470

East Asian (EAS) AF: 0.123 AC: 634 AN: 5170

South Asian (SAS) AF: 0.102 AC: 491 AN: 4822

European-Finnish (FIN) AF: 0.0979 AC: 1035 AN: 10572

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6612 AN: 68010

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.0984 Hom.: 1364

Bravo AF: 0.118

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.52
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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: rs9362399; hg19: chr6-87874389;