chr9-113422578-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001278629.2(C9orf43):​c.476C>T​(p.Ser159Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

C9orf43
NM_001278629.2 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18
Variant links:
Genes affected
C9orf43 (HGNC:23570): (chromosome 9 open reading frame 43)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.024040103).
BP6
Variant 9-113422578-C-T is Benign according to our data. Variant chr9-113422578-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2376280.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C9orf43NM_001278629.2 linkuse as main transcriptc.476C>T p.Ser159Leu missense_variant 6/14 ENST00000374165.6 NP_001265558.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C9orf43ENST00000374165.6 linkuse as main transcriptc.476C>T p.Ser159Leu missense_variant 6/141 NM_001278629.2 ENSP00000363280 P1
C9orf43ENST00000288462.4 linkuse as main transcriptc.476C>T p.Ser159Leu missense_variant 6/141 ENSP00000288462 P1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.0000836
AC:
21
AN:
251084
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135704
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000458
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000529
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461610
Hom.:
1
Cov.:
31
AF XY:
0.0000550
AC XY:
40
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000394
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000906
AC:
11

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 06, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.051
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.14
DANN
Benign
0.11
DEOGEN2
Benign
0.0035
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0089
N
LIST_S2
Benign
0.50
.;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.024
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.080
N;N
MutationTaster
Benign
1.0
N;N
PROVEAN
Benign
-0.69
N;N
REVEL
Benign
0.0070
Sift
Benign
1.0
T;T
Sift4G
Benign
0.61
T;T
Polyphen
0.0010
B;B
Vest4
0.12
MVP
0.095
MPC
0.078
ClinPred
0.014
T
GERP RS
-6.5
Varity_R
0.028
gMVP
0.036

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

LitVar

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

Other links and lift over

dbSNP: rs201811495; hg19: chr9-116184858; API