9-34552686-C-T

Variant names:

• chr9-34552686-C-T
• rs148059931
• NM_147164.3:c.937G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_147164.3(CNTFR):​c.937G>A​(p.Ala313Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. A313S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTFR NM_147164.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

CNTFR (HGNC:2170): (ciliary neurotrophic factor receptor) This gene encodes a member of the type 1 cytokine receptor family. The encoded protein is the ligand-specific component of a tripartite receptor for ciliary neurotrophic factor, which plays a critical role in neuronal cell survival, differentiation and gene expression. Binding of ciliary neurotrophic factor to the encoded protein recruits the transmembrane components of the receptor, gp130 and leukemia inhibitory factor receptor, facilitating signal transduction. Single nucleotide polymorphisms in this gene may be associated with variations in muscle strength, as well as early onset of eating disorders. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13182104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147164.3. 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
	CNTFR	NM_147164.3	MANE Select	c.937G>A	p.Ala313Thr	missense	Exon 8 of 10	NP_671693.1	P26992
	CNTFR	NM_001207011.2		c.937G>A	p.Ala313Thr	missense	Exon 8 of 10	NP_001193940.1	P26992
	CNTFR	NM_001842.5		c.937G>A	p.Ala313Thr	missense	Exon 7 of 9	NP_001833.1	P26992

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTFR	ENST00000378980.8	TSL:1 MANE Select	c.937G>A	p.Ala313Thr	missense	Exon 8 of 10	ENSP00000368265.3	P26992
	CNTFR	ENST00000351266.8	TSL:1	c.937G>A	p.Ala313Thr	missense	Exon 7 of 9	ENSP00000242338.4	P26992
	CNTFR	ENST00000868706.1		c.937G>A	p.Ala313Thr	missense	Exon 8 of 10	ENSP00000538765.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.079
Sift	Benign	0.31	T
Sift4G	Benign	0.41	T
Polyphen		0.011	B
Vest4		0.19
MutPred		0.20		Gain of glycosylation at A313 (P = 0.0017)
MVP		0.27
MPC		0.42
ClinPred		0.26	T
GERP RS		4.6
Varity_R		0.062
gMVP		0.46

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

Other links and lift over

dbSNP: rs148059931; hg19: chr9-34552684;