NM_017998.3:c.462G>T

Variant names:

• chr9-74948171-C-A
• rs2769058
• NM_017998.3:c.462G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017998.3(C9orf40):​c.462G>T​(p.Gln154His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C9orf40 NM_017998.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 20 publications found

Genes affected

C9orf40 (HGNC:23433): (chromosome 9 open reading frame 40)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017998.3. 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
	C9orf40	NM_017998.3	MANE Select	c.462G>T	p.Gln154His	missense	Exon 2 of 2	NP_060468.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C9orf40	ENST00000376854.6	TSL:1 MANE Select	c.462G>T	p.Gln154His	missense	Exon 2 of 2	ENSP00000366050.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0073	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.99
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.37		Gain of phosphorylation at Y150 (P = 0.2312)
MVP		0.45
MPC		1.8
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.34
gMVP		0.18
Mutation Taster		=91/9	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: rs2769058; hg19: chr9-77563087;