rs765544741

Variant names:

• chr9-113419113-C-G
• rs765544741
• NM_001278629.2:c.293C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-113419113-C-G
• chr9-113419113-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001278629.2(C9orf43):​c.293C>G​(p.Pro98Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P98L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C9orf43 NM_001278629.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 0 publications found

Genes affected

C9orf43 (HGNC:23570): (chromosome 9 open reading frame 43)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024884641).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278629.2. 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
	C9orf43	NM_001278629.2	MANE Select	c.293C>G	p.Pro98Arg	missense	Exon 4 of 14	NP_001265558.1	Q8TAL5
	C9orf43	NM_001278630.2		c.347C>G	p.Pro116Arg	missense	Exon 4 of 14	NP_001265559.1
	C9orf43	NM_152786.3		c.293C>G	p.Pro98Arg	missense	Exon 4 of 14	NP_689999.1	Q8TAL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C9orf43	ENST00000374165.6	TSL:1 MANE Select	c.293C>G	p.Pro98Arg	missense	Exon 4 of 14	ENSP00000363280.1	Q8TAL5
	C9orf43	ENST00000288462.4	TSL:1	c.293C>G	p.Pro98Arg	missense	Exon 4 of 14	ENSP00000288462.4	Q8TAL5
	C9orf43	ENST00000940447.1		c.293C>G	p.Pro98Arg	missense	Exon 4 of 14	ENSP00000610506.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247722 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456810 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724510

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.0000227 AC: 1 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 84938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109616

Other (OTH) AF: 0.00 AC: 0 AN: 60212

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.31
DANN	Benign	0.63
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.5
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.012
Sift	Benign	0.61	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.085
MutPred		0.20		Loss of catalytic residue at P97 (P = 0.0135)
MVP		0.099
MPC		0.16
ClinPred		0.038	T
GERP RS		-9.0
Varity_R		0.031
gMVP		0.037
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs765544741; hg19: chr9-116181393;