NM_001803.3:c.43G>A

Variant names:

• chr1-26318060-G-A
• rs369012932
• NM_001803.3:c.43G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001803.3(CD52):​c.43G>A​(p.Val15Ile) 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. 16/21 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. V15L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD52 NM_001803.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 0 publications found

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]

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]

ACMG classification

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=0.04983619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD52	NM_001803.3	c.43G>A	p.Val15Ile	missense_variant	Exon 1 of 2	ENST00000374213.3	NP_001794.2
UBXN11	NM_145345.3	c.-162C>T		5_prime_UTR_variant	Exon 1 of 15		NP_663320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD52	ENST00000374213.3	c.43G>A	p.Val15Ile	missense_variant	Exon 1 of 2	1	NM_001803.3	ENSP00000363330.2
CD52	ENST00000492808.5	n.103G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
CD52	ENST00000470468.1	n.103G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
UBXN11	ENST00000374217.7	c.-162C>T		5_prime_UTR_variant	Exon 1 of 15	2		ENSP00000363334.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.3
DANN	Benign	0.88
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.75
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.061
Sift	Benign	0.28	T
Sift4G	Benign	0.38	T
Polyphen		0.080	B
Vest4		0.12
MutPred		0.18		Loss of catalytic residue at V15 (P = 0.0631);
MVP		0.27
MPC		0.26
ClinPred		0.17	T
GERP RS		-5.5
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.064
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369012932; hg19: chr1-26644551;