chr5-77077644-C-G

Position:

• chr5-77077644-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032367.4(ZBED3):​c.235G>C​(p.Gly79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,258,684 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: ZBED3 NM_032367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.785

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.301857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBED3	NM_032367.4	c.235G>C	p.Gly79Arg	missense_variant	3/3	ENST00000255198.3
ZBED3	NM_001329564.2	c.235G>C	p.Gly79Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBED3	ENST00000255198.3	c.235G>C	p.Gly79Arg	missense_variant	3/3	1	NM_032367.4	P1
ZBED3	ENST00000511587.1	c.235G>C	p.Gly79Arg	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000318 AC: 4 AN: 1258684 Hom.: 0 Cov.: 31 AF XY: 0.00000323 AC XY: 2 AN XY: 619424

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: 0.0000633

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2023

The c.235G>C (p.G79R) 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 235, causing the glycine (G) at amino acid position 79 to be replaced by an arginine (R). 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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.55	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.097
Sift	Benign	0.066	T;D
Sift4G	Benign	0.13	T;.
Polyphen		0.98	D;.
Vest4		0.19
MutPred		0.55		Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);
MVP		0.15
MPC		2.8
ClinPred		0.98	D
GERP RS		1.4
Varity_R		0.16
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs546975061; hg19: chr5-76373469;