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GeneBe

5-39341267-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong

The NM_001737.5(C9):c.355T>C(p.Cys119Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. C119G) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

C9
NM_001737.5 missense

Scores

12
5
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27
Variant links:
Genes affected
C9 (HGNC:1358): (complement C9) This gene encodes the final component of the complement system. It participates in the formation of the Membrane Attack Complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause component C9 deficiency. [provided by RefSeq, Feb 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr5-39341267-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 17042.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=2}.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C9NM_001737.5 linkuse as main transcriptc.355T>C p.Cys119Arg missense_variant 4/11 ENST00000263408.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C9ENST00000263408.5 linkuse as main transcriptc.355T>C p.Cys119Arg missense_variant 4/111 NM_001737.5 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.54
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.70
D
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.98
D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Pathogenic
4.6
H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-11
D
REVEL
Pathogenic
0.93
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.99
MutPred
0.86
Gain of MoRF binding (P = 0.0145);
MVP
0.95
MPC
0.31
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.99
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121909593; hg19: chr5-39341369; API