chr5-77077503-C-T

Variant names:

• chr5-77077503-C-T
• rs911403053
• NM_032367.4:c.376G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032367.4(ZBED3):​c.376G>A​(p.Glu126Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,193,066 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ZBED3 NM_032367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37205756).

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.376G>A	p.Glu126Lys	missense	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.376G>A	p.Glu126Lys	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.376G>A	p.Glu126Lys	missense	Exon 3 of 3	ENSP00000255198.2	Q96IU2
	ENSG00000285000	ENST00000646704.1		n.1809+15701C>T		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
	ZBED3	ENST00000896398.1		c.376G>A	p.Glu126Lys	missense	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes AF: 0.0000934 AC: 14 AN: 149942 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000164

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 160 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 105 AN: 1043124 Hom.: 0 Cov.: 31 AF XY: 0.0000989 AC XY: 49 AN XY: 495374

African (AFR) AF: 0.00 AC: 0 AN: 21114

American (AMR) AF: 0.00 AC: 0 AN: 6868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11978

East Asian (EAS) AF: 0.00 AC: 0 AN: 22054

South Asian (SAS) AF: 0.00 AC: 0 AN: 19706

European-Finnish (FIN) AF: 0.0000509 AC: 1 AN: 19648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2684

European-Non Finnish (NFE) AF: 0.000113 AC: 102 AN: 898892

Other (OTH) AF: 0.0000498 AC: 2 AN: 40180

GnomAD4 genome AF: 0.0000934 AC: 14 AN: 149942 Hom.: 0 Cov.: 32 AF XY: 0.0000821 AC XY: 6 AN XY: 73124

African (AFR) AF: 0.0000243 AC: 1 AN: 41182

American (AMR) AF: 0.0000664 AC: 1 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000102 AC: 1 AN: 9814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000164 AC: 11 AN: 67178

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.000324 Hom.: 0

Bravo AF: 0.000106

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	Uncertain	0.48
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.15		Gain of ubiquitination at E126 (P = 0.009)
MVP		0.30
MPC		1.7
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.48
gMVP		0.17
Mutation Taster		=94/6	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

dbSNP: rs911403053; hg19: chr5-76373328;