rs12135160

chr1-207337350-C-T

Variant summary

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

The NM_000574.5(CD55):c.1001C>T(p.Ser334Phe) 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. 13/21 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. S334P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD55 NM_000574.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

Genes affected

CD55 (HGNC:2665): (CD55 molecule (Cromer blood group)) This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. Antigens present on this protein constitute the Cromer blood group system (CROM). Alternative splicing results in multiple transcript variants. The predominant transcript variant encodes a membrane-bound protein, but alternatively spliced transcripts may produce soluble proteins. [provided by RefSeq, Jul 2014]

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=0.15342739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD55	NM_000574.5	c.1001C>T	p.Ser334Phe	missense_variant	8/10	ENST00000367064.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000367064.9	c.1001C>T	p.Ser334Phe	missense_variant	8/10	1	NM_000574.5	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;T;.;.;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.84	T;T;T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;.;.;M;M;.;M
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N;N;N;.;N;.;.
REVEL	Benign	0.027
Sift	Uncertain	0.0070	D;D;D;.;D;.;.
Sift4G	Uncertain	0.047	D;D;D;.;D;D;.
Polyphen		0.13	B;B;B;.;B;.;.
Vest4		0.16
MutPred		0.34		Loss of glycosylation at S334 (P = 0.0105);Loss of glycosylation at S334 (P = 0.0105);.;Loss of glycosylation at S334 (P = 0.0105);Loss of glycosylation at S334 (P = 0.0105);.;Loss of glycosylation at S334 (P = 0.0105);
MVP		0.25
MPC		0.55
ClinPred		0.65	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.095

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12135160; hg19: chr1-207510695; COSMIC: COSV58576732; COSMIC: COSV58576732;