NM_147164.3:c.364C>T

Variant names:

• chr9-34557940-G-A
• NM_147164.3:c.364C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_147164.3(CNTFR):​c.364C>T​(p.Pro122Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTFR NM_147164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.04
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

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.364C>T	p.Pro122Ser	missense	Exon 5 of 10	NP_671693.1	P26992
	CNTFR	NM_001207011.2		c.364C>T	p.Pro122Ser	missense	Exon 5 of 10	NP_001193940.1	P26992
	CNTFR	NM_001842.5		c.364C>T	p.Pro122Ser	missense	Exon 4 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.364C>T	p.Pro122Ser	missense	Exon 5 of 10	ENSP00000368265.3	P26992
	CNTFR	ENST00000351266.8	TSL:1	c.364C>T	p.Pro122Ser	missense	Exon 4 of 9	ENSP00000242338.4	P26992
	CNTFR	ENST00000868706.1		c.364C>T	p.Pro122Ser	missense	Exon 5 of 10	ENSP00000538765.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1420110 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 701954

African (AFR) AF: 0.00 AC: 0 AN: 32248

American (AMR) AF: 0.00 AC: 0 AN: 39570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 78608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091190

Other (OTH) AF: 0.00 AC: 0 AN: 58616

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		9.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.30
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.64		Loss of sheet (P = 0.0315)
MVP		0.51
MPC		1.0
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.72

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

hg19: chr9-34557938;