rs386833767

Variant summary

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

The NM_001081.4(CUBN):​c.1436C>T​(p.Ser479Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CUBN
NM_001081.4 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.53
Variant links:
Genes affected
CUBN (HGNC:2548): (cubilin) Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. [provided by RefSeq, Jul 2008]

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, 0.822

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CUBNNM_001081.4 linkuse as main transcriptc.1436C>T p.Ser479Leu missense_variant 13/67 ENST00000377833.10 NP_001072.2 O60494
CUBNXM_011519708.3 linkuse as main transcriptc.1436C>T p.Ser479Leu missense_variant 13/55 XP_011518010.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUBNENST00000377833.10 linkuse as main transcriptc.1436C>T p.Ser479Leu missense_variant 13/671 NM_001081.4 ENSP00000367064.4 O60494

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1459326
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
726130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Uncertain
0.052
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.34
Sift
Benign
0.032
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.99
D
Vest4
0.70
MutPred
0.53
Loss of disorder (P = 0.0093);
MVP
0.84
MPC
0.39
ClinPred
0.94
D
GERP RS
5.7
Varity_R
0.15
gMVP
0.37

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs386833767; hg19: chr10-17145218; COSMIC: COSV64720108; API