rs911403053

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-77077503-C-G
• chr5-77077503-C-T

Variant summary

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

The NM_032367.4(ZBED3):​c.376G>C​(p.Glu126Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,043,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E126K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZBED3 NM_032367.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34788987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBED3	NM_032367.4	c.376G>C	p.Glu126Gln	missense_variant	Exon 3 of 3	ENST00000255198.3	NP_115743.1
ZBED3	NM_001329564.2	c.376G>C	p.Glu126Gln	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.376G>C	p.Glu126Gln	missense_variant	Exon 3 of 3	1	NM_032367.4	ENSP00000255198.2
ENSG00000285000	ENST00000646704.1	n.1809+15701C>G		intron_variant	Intron 13 of 15			ENSP00000495089.1
ZBED3	ENST00000511587.1	c.376G>C	p.Glu126Gln	missense_variant	Exon 2 of 2	3		ENSP00000427487.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 5 AN: 1043124 Hom.: 0 Cov.: 31 AF XY: 0.00000202 AC XY: 1 AN XY: 495374

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: 0.00000556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.55	T;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.31
MutPred		0.087		Gain of MoRF binding (P = 0.0519);Gain of MoRF binding (P = 0.0519);
MVP		0.22
MPC		1.8
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.48
gMVP		0.10

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: rs911403053; hg19: chr5-76373328;