chr11-10853430-A-T

Position:

• chr11-10853430-A-T

Variant summary

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

The ENST00000413761.7(ZBED5):​c.1516T>A​(p.Ser506Thr) 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. 14/19 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)
• Consequence: ZBED5 ENST00000413761.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

Genes affected

ZBED5 (HGNC:30803): (zinc finger BED-type containing 5) This gene is unusual in that its coding sequence is mostly derived from Charlie-like DNA transposon; however, it does not appear to be an active DNA transposon as it is not flanked by terminal inverted repeats. The encoded protein is conserved among the mammalian Laurasiatheria branch. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2009]

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=0.24235797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED5	NM_001143667.2	c.1516T>A	p.Ser506Thr	missense_variant	3/3	ENST00000413761.7	NP_001137139.1
ZBED5	NM_021211.4	c.1516T>A	p.Ser506Thr	missense_variant	3/3		NP_067034.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBED5	ENST00000413761.7	c.1516T>A	p.Ser506Thr	missense_variant	3/3	1	NM_001143667.2	ENSP00000415939	P1
ZBED5	ENST00000432999.6	c.1516T>A	p.Ser506Thr	missense_variant	3/3	1		ENSP00000398106	P1
ZBED5	ENST00000525350.5	n.75+2714T>A		intron_variant, non_coding_transcript_variant		2
ZBED5	ENST00000533925.5	n.326+2714T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 11, 2024

The c.1516T>A (p.S506T) alteration is located in exon 3 (coding exon 1) of the ZBED5 gene. This alteration results from a T to A substitution at nucleotide position 1516, causing the serine (S) at amino acid position 506 to be replaced by a threonine (T). 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	0.080
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0084	T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.57	.;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	0.97	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.74	N;N
REVEL	Benign	0.057
Sift	Benign	0.35	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.92	P;P
Vest4		0.33
MutPred		0.32		Gain of MoRF binding (P = 0.2222);Gain of MoRF binding (P = 0.2222);
MVP		0.17
ClinPred		0.35	T
GERP RS		4.0
Varity_R		0.071
gMVP		0.16

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: chr11-10874977;