chr5-77077662-C-G

Variant names:

• chr5-77077662-C-G
• NM_032367.4:c.217G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032367.4(ZBED3):​c.217G>C​(p.Gly73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,251,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G73A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: ZBED3 NM_032367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

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.217G>C	p.Gly73Arg	missense	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.217G>C	p.Gly73Arg	missense	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.217G>C	p.Gly73Arg	missense	Exon 3 of 3	ENSP00000255198.2	Q96IU2
	ENSG00000285000	ENST00000646704.1		n.1809+15860C>G		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
	ZBED3	ENST00000896398.1		c.217G>C	p.Gly73Arg	missense	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1251656 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 615376

African (AFR) AF: 0.00 AC: 0 AN: 25316

American (AMR) AF: 0.00 AC: 0 AN: 19474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20462

East Asian (EAS) AF: 0.00 AC: 0 AN: 27182

South Asian (SAS) AF: 0.0000162 AC: 1 AN: 61674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3580

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012684

Other (OTH) AF: 0.00 AC: 0 AN: 51092

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.81		Gain of solvent accessibility (P = 0.0171)
MVP		0.095
MPC		2.8
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.58
gMVP		0.12
Mutation Taster		=96/4	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

hg19: chr5-76373487;