5-77077593-C-T

Variant names:

• chr5-77077593-C-T
• NM_032367.4:c.286G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032367.4(ZBED3):​c.286G>A​(p.Ala96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,199,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: ZBED3 NM_032367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.400
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117316335).

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.286G>A	p.Ala96Thr	missense	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.286G>A	p.Ala96Thr	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.286G>A	p.Ala96Thr	missense	Exon 3 of 3	ENSP00000255198.2	Q96IU2
	ENSG00000285000	ENST00000646704.1		n.1809+15791C>T		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
	ZBED3	ENST00000896398.1		c.286G>A	p.Ala96Thr	missense	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000250 AC: 3 AN: 1199818 Hom.: 0 Cov.: 31 AF XY: 0.00000511 AC XY: 3 AN XY: 587232

African (AFR) AF: 0.00 AC: 0 AN: 24782

American (AMR) AF: 0.00 AC: 0 AN: 18528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19196

East Asian (EAS) AF: 0.00 AC: 0 AN: 26410

South Asian (SAS) AF: 0.0000397 AC: 2 AN: 50354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3352

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 981948

Other (OTH) AF: 0.00 AC: 0 AN: 48154

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	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.40
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.070	N
REVEL	Benign	0.067
Sift	Benign	0.59	T
Sift4G	Benign	0.42	T
Polyphen		0.98	D
Vest4		0.054
MutPred		0.33		Gain of phosphorylation at A96 (P = 0.0183)
MVP		0.13
MPC		1.6
ClinPred		0.34	T
GERP RS		1.2
Varity_R		0.066
gMVP		0.041
Mutation Taster		=98/2	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

hg19: chr5-76373418;