11-33710237-GTC-ATT

Variant names:

• chr11-33710237-GTC-ATT
• NM_000611.6:c.274_276delGACinsAAT
• CD59 p.Asp92Asn

Variant summary

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

The NM_000611.6(CD59):​c.274_276delGACinsAAT​(p.Asp92Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD59 NM_000611.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

CD59 (HGNC:1689): (CD59 molecule (CD59 blood group)) This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

CD59 Gene-Disease associations (from GenCC):

• primary CD59 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000284969 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000611.6. 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
	CD59	NM_000611.6	MANE Select	c.274_276delGACinsAAT	p.Asp92Asn	missense	N/A	NP_000602.1	Q6FHM9
	CD59	NM_001127223.1		c.274_276delGACinsAAT	p.Asp92Asn	missense	N/A	NP_001120695.1	Q6FHM9
	CD59	NM_001127225.2		c.274_276delGACinsAAT	p.Asp92Asn	missense	N/A	NP_001120697.1	P13987-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD59	ENST00000642928.2	MANE Select	c.274_276delGACinsAAT	p.Asp92Asn	missense	N/A	ENSP00000494884.1	P13987-1
	ENSG00000284969	ENST00000534312.5	TSL:3	c.274_276delGACinsAAT	p.Asp92Asn	missense	N/A	ENSP00000432362.1
	CD59	ENST00000395850.9	TSL:1	c.274_276delGACinsAAT	p.Asp92Asn	missense	N/A	ENSP00000379191.3	P13987-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-33731783;