5-77077659-C-A

Variant names:

• chr5-77077659-C-A
• rs749458270
• NM_032367.4:c.220G>T

Variant summary

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

The NM_032367.4(ZBED3):​c.220G>T​(p.Glu74*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000797 in 1,254,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: ZBED3 NM_032367.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 0 publications found

Genes affected

ZBED3 (HGNC:20711): (zinc finger BED-type containing 3) This gene belongs to a class of genes that arose through hAT DNA transposition and that encode regulatory proteins. This gene is upregulated in lung cancer tissues, where the encoded protein causes an accumulation of beta-catenin and enhanced lung cancer cell invasion. In addition, the encoded protein can be secreted and be involved in resistance to insulin. [provided by RefSeq, Jul 2016]

ENSG00000285000 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED3	NM_032367.4	MANE Select	c.220G>T	p.Glu74*	stop_gained	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.220G>T	p.Glu74*	stop_gained	Exon 2 of 2	NP_001316493.1	Q96IU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED3	ENST00000255198.3	TSL:1 MANE Select	c.220G>T	p.Glu74*	stop_gained	Exon 3 of 3	ENSP00000255198.2	Q96IU2
	ENSG00000285000	ENST00000646704.1		n.1809+15857C>A		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
	ZBED3	ENST00000896398.1		c.220G>T	p.Glu74*	stop_gained	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1254876 Hom.: 0 Cov.: 32 AF XY: 0.00000162 AC XY: 1 AN XY: 617192

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25420

American (AMR) AF: 0.00 AC: 0 AN: 20192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20730

East Asian (EAS) AF: 0.00 AC: 0 AN: 27160

South Asian (SAS) AF: 0.00 AC: 0 AN: 62270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3600

European-Non Finnish (NFE) AF: 9.86e-7 AC: 1 AN: 1013912

Other (OTH) AF: 0.00 AC: 0 AN: 51254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.031	N
PhyloP100		0.0070
Vest4		0.038
GERP RS		1.2
Mutation Taster		=111/89	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749458270; hg19: chr5-76373484;