5-77077649-C-G

Variant names:

• chr5-77077649-C-G
• NM_032367.4:c.230G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032367.4(ZBED3):​c.230G>C​(p.Gly77Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBED3 NM_032367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23139295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBED3	NM_032367.4	c.230G>C	p.Gly77Ala	missense_variant	Exon 3 of 3	ENST00000255198.3	NP_115743.1
ZBED3	NM_001329564.2	c.230G>C	p.Gly77Ala	missense_variant	Exon 2 of 2		NP_001316493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBED3	ENST00000255198.3	c.230G>C	p.Gly77Ala	missense_variant	Exon 3 of 3	1	NM_032367.4	ENSP00000255198.2
ENSG00000285000	ENST00000646704.1	n.1809+15847C>G		intron_variant	Intron 13 of 15			ENSP00000495089.1
ZBED3	ENST00000511587.1	c.230G>C	p.Gly77Ala	missense_variant	Exon 2 of 2	3		ENSP00000427487.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1257612 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 618734

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230G>C (p.G77A) alteration is located in exon 3 (coding exon 1) of the ZBED3 gene. This alteration results from a G to C substitution at nucleotide position 230, causing the glycine (G) at amino acid position 77 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0079	T;.
Eigen	Benign	-0.059
Eigen_PC	Benign	0.058
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.60	T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.067
Sift	Benign	0.12	T;T
Sift4G	Benign	0.16	T;.
Polyphen		0.41	B;.
Vest4		0.077
MutPred		0.50		Loss of catalytic residue at G77 (P = 0.0507);Loss of catalytic residue at G77 (P = 0.0507);
MVP		0.040
MPC		1.6
ClinPred		0.54	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.074

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-76373474;