9-34564826-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_147164.3(CNTFR):c.92C>T(p.Pro31Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTFR NM_147164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23272777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTFR	NM_147164.3	c.92C>T	p.Pro31Leu	missense_variant	4/10	ENST00000378980.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTFR	ENST00000378980.8	c.92C>T	p.Pro31Leu	missense_variant	4/10	1	NM_147164.3	P1
CNTFR	ENST00000351266.8	c.92C>T	p.Pro31Leu	missense_variant	3/9	1		P1
CNTFR	ENST00000610543.4	c.92C>T	p.Pro31Leu	missense_variant	4/10	5		P1
CNTFR	ENST00000417345.2	c.92C>T	p.Pro31Leu	missense_variant	4/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.92C>T (p.P31L) alteration is located in exon 4 (coding exon 2) of the CNTFR gene. This alteration results from a C to T substitution at nucleotide position 92, causing the proline (P) at amino acid position 31 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.024
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;D;.;N
REVEL	Benign	0.086
Sift	Uncertain	0.0080	D;D;.;D
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.069	B;B;B;.
Vest4		0.61
MutPred		0.37		Loss of disorder (P = 0.0327);Loss of disorder (P = 0.0327);Loss of disorder (P = 0.0327);Loss of disorder (P = 0.0327);
MVP		0.32
MPC		0.41
ClinPred		0.84	D
GERP RS		3.5
Varity_R		0.13
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34564824;