5-39331792-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001737.5(C9):c.499C>T(p.Pro167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 1,612,936 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 62 hom. )

Consequence

C9
NM_001737.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 3.28

Publications

49 publications found

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]

C9 Gene-Disease associations (from GenCC):

complement component 9 deficiency
Inheritance: Unknown, AR Classification: STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

C9 links:

ENSG00000289699 (HGNC:):

ENSG00000289699 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009836942).

BP6

Variant 5-39331792-G-A is Benign according to our data. Variant chr5-39331792-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 92120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001737.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C9	NM_001737.5	MANE Select	c.499C>T	p.Pro167Ser	missense	Exon 5 of 11	NP_001728.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
C9	ENST00000263408.5	TSL:1 MANE Select	c.499C>T	p.Pro167Ser	missense	Exon 5 of 11	ENSP00000263408.4
C9	ENST00000509186.6	TSL:3	c.427C>T	p.Pro143Ser	missense	Exon 5 of 11	ENSP00000512235.1
C9	ENST00000695880.1		c.499C>T	p.Pro167Ser	missense	Exon 5 of 10	ENSP00000512236.1

Frequencies

GnomAD3 genomes

AF:

0.00595

AC:

905

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00510

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00982

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00519

AC:

1306

AN:

251480

AF XY:

0.00523

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.00805

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00787

AC:

11499

AN:

1460682

Hom.:

Cov.:

AF XY:

0.00767

AC XY:

5573

AN XY:

726718

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

33462

American (AMR)

AF:

0.00546

AC:

244

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00291

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000962

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00335

AC:

179

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00948

AC:

10526

AN:

1110898

Other (OTH)

AF:

0.00550

AC:

332

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

523

1046

1569

2092

2615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00594

AC:

905

AN:

152254

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

410

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41552

American (AMR)

AF:

0.00373

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00510

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00982

AC:

668

AN:

68028

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00845

Hom.:

Bravo

AF:

0.00548

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00471

AC:

572

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00806

ClinVar

Significance: Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

C9: BS2; ENSG00000289699: BS2

Age related macular degeneration 15

Other:1

Nov 01, 2013

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

M_CAP

Benign

0.021

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.8

PhyloP100

3.3

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.50

MVP

0.72

MPC

0.25

ClinPred

0.024

GERP RS

3.8

Varity_R

0.89

gMVP

0.84

Mutation Taster

=84/16

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over