rs774219978

Variant names:

• chr11-10853057-C-A
• rs774219978
• NM_001143667.2:c.1889G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-10853057-C-A
• chr11-10853057-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143667.2(ZBED5):​c.1889G>T​(p.Arg630Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R630C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZBED5 NM_001143667.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2623033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143667.2. 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
	ZBED5	NM_001143667.2	MANE Select	c.1889G>T	p.Arg630Leu	missense	Exon 3 of 3	NP_001137139.1	Q49AG3
	ZBED5	NM_021211.4		c.1889G>T	p.Arg630Leu	missense	Exon 3 of 3	NP_067034.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED5	ENST00000413761.7	TSL:1 MANE Select	c.1889G>T	p.Arg630Leu	missense	Exon 3 of 3	ENSP00000415939.2	Q49AG3
	ZBED5	ENST00000432999.6	TSL:1	c.1889G>T	p.Arg630Leu	missense	Exon 3 of 3	ENSP00000398106.2	Q49AG3
	ZBED5	ENST00000876894.1		c.1889G>T	p.Arg630Leu	missense	Exon 2 of 2	ENSP00000546953.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399266 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690122

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078854

Other (OTH) AF: 0.00 AC: 0 AN: 57992

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N
PhyloP100		0.90
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.19
Sift	Benign	0.25	T
Sift4G	Benign	0.22	T
Polyphen		0.16	B
Vest4		0.56
MutPred		0.57		Loss of MoRF binding (P = 0.0702)
MVP		0.17
ClinPred		0.22	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.78
Mutation Taster		=97/3	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: rs774219978; hg19: chr11-10874604;