Genetic Variant CD52:p.Val17Leu (chr1-26318066-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001803.3(CD52):c.49G>C(p.Val17Leu) 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. 15/21 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

CD52
NM_001803.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

Publications

0 publications found

Variant links:

Genes affected

CD52 (HGNC:1804): (CD52 molecule) Involved in positive regulation of cytosolic calcium ion concentration. Predicted to be located in extracellular region and plasma membrane. Predicted to be intrinsic component of plasma membrane. Predicted to be active in sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

CD52 links:

UBXN11 (HGNC:30600): (UBX domain protein 11) This gene encodes a protein with a divergent C-terminal UBX domain. The homologous protein in the rat interacts with members of the Rnd subfamily of Rho GTPases at the cell periphery through its C-terminal region. It also interacts with several heterotrimeric G proteins through their G-alpha subunits and promotes Rho GTPase activation. It is proposed to serve a bidirectional role in the promotion and inhibition of Rho activity through upstream signaling pathways. The 3' coding sequence of this gene contains a polymoprhic region of 24 nt tandem repeats. Several transcripts containing between 1.5 and five repeat units have been reported. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UBXN11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056001276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001803.3. 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
	CD52	NM_001803.3	MANE Select	c.49G>C	p.Val17Leu	missense	Exon 1 of 2	NP_001794.2	P31358
	UBXN11	NM_145345.3		c.-168C>G		5_prime_UTR	Exon 1 of 15	NP_663320.2	Q5T124-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD52	ENST00000374213.3	TSL:1 MANE Select	c.49G>C	p.Val17Leu	missense	Exon 1 of 2	ENSP00000363330.2	P31358
CD52	ENST00000492808.5	TSL:1	n.109G>C		non_coding_transcript_exon	Exon 1 of 2
UBXN11	ENST00000374217.7	TSL:2	c.-168C>G		5_prime_UTR	Exon 1 of 15	ENSP00000363334.2	Q5T124-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.8

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.14

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.48

M_CAP

Benign

0.0043

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.1

PhyloP100

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.018

Sift

Benign

0.060

Sift4G

Benign

0.29

Polyphen

0.0030

Vest4

0.14

MutPred

0.18

Gain of disorder (P = 0.1938)

MVP

0.30

MPC

0.31

ClinPred

0.20

GERP RS

-4.8

PromoterAI

-0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.11

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over