18-48711629-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014772.3(CTIF):​c.518C>T​(p.Pro173Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CTIF
NM_014772.3 missense

Scores

3
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23
Variant links:
Genes affected
CTIF (HGNC:23925): (cap binding complex dependent translation initiation factor) CTIF is a component of the CBP80 (NCBP1; MIM 600469)/CBP20 (NCBP2; MIM 605133) translation initiation complex that binds cotranscriptionally to the cap end of nascent mRNA. The CBP80/CBP20 complex is involved in a simultaneous editing and translation step that recognizes premature termination codons (PTCs) in mRNAs and directs PTC-containing mRNAs toward nonsense-mediated decay (NMD). On mRNAs without PTCs, the CBP80/CBP20 complex is replaced with cytoplasmic mRNA cap-binding proteins, including EIF4G (MIM 600495), and steady-state translation of the mRNAs resumes in the cytoplasm (Kim et al., 2009 [PubMed 19648179]).[supplied by OMIM, Dec 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTIFNM_014772.3 linkc.518C>T p.Pro173Leu missense_variant Exon 7 of 12 ENST00000256413.8 NP_055587.1 O43310-1A0A024R259

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTIFENST00000256413.8 linkc.518C>T p.Pro173Leu missense_variant Exon 7 of 12 1 NM_014772.3 ENSP00000256413.3 O43310-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461720
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000277
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.518C>T (p.P173L) alteration is located in exon 8 (coding exon 6) of the CTIF gene. This alteration results from a C to T substitution at nucleotide position 518, causing the proline (P) at amino acid position 173 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
0.17
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Benign
0.74
D
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.80
D;D;D
MetaSVM
Uncertain
0.085
D
MutationAssessor
Benign
1.1
L;L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.4
D;D;.
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.92
MutPred
0.67
Loss of disorder (P = 0.057);Loss of disorder (P = 0.057);Loss of disorder (P = 0.057);
MVP
0.58
MPC
0.59
ClinPred
0.99
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.49
gMVP
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777361464; hg19: chr18-46238000; API