6-87155630-C-T

Position:

• chr6-87155630-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The ENST00000369577.8(ZNF292):​c.39C>T​(p.Cys13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF292 ENST00000369577.8 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.822

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21827966).
• BP6: Variant 6-87155630-C-T is Benign according to our data. Variant chr6-87155630-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3055234.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF292	NM_015021.3	c.39C>T	p.Cys13=	synonymous_variant	1/8	ENST00000369577.8	NP_055836.1
ZNF292	NM_001351444.2	c.-527C>T		5_prime_UTR_variant	1/9		NP_001338373.1
ZNF292	XM_047418459.1	c.-695C>T		5_prime_UTR_variant	1/10		XP_047274415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF292	ENST00000369577.8	c.39C>T	p.Cys13=	synonymous_variant	1/8	1	NM_015021.3	ENSP00000358590	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429352 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707784

Gnomad4 AFR exome AF: 0.0000304

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: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZNF292-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 04, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.61	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
MutPred		0.27		Loss of methylation at R4 (P = 0.0189);
MVP		0.39
ClinPred		0.73	D
GERP RS		3.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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

LitVar

Other links and lift over

dbSNP: rs1770498812; hg19: chr6-87865348;