GeneBe

rs144039014

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001396959.1(TBC1D1):​c.45C>G​(p.Asn15Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N15N) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

TBC1D1
NM_001396959.1 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

0 publications found
Variant links:
Genes affected
TBC1D1 (HGNC:11578): (TBC1 domain family member 1) TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]
TBC1D1 Gene-Disease associations (from GenCC):
  • non-syndromic renal or urinary tract malformation
    Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
  • congenital anomaly of kidney and urinary tract
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

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=0.10831636).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396959.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TBC1D1
NM_001396959.1
MANE Select
c.45C>Gp.Asn15Lys
missense
Exon 2 of 22NP_001383888.1A0A8V8TNS9
TBC1D1
NM_015173.4
c.45C>Gp.Asn15Lys
missense
Exon 2 of 20NP_055988.2
TBC1D1
NM_001253912.2
c.45C>Gp.Asn15Lys
missense
Exon 2 of 21NP_001240841.1Q86TI0-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TBC1D1
ENST00000698857.1
MANE Select
c.45C>Gp.Asn15Lys
missense
Exon 2 of 22ENSP00000513987.1A0A8V8TNS9
TBC1D1
ENST00000261439.9
TSL:1
c.45C>Gp.Asn15Lys
missense
Exon 2 of 20ENSP00000261439.4Q86TI0-1
TBC1D1
ENST00000961338.1
c.45C>Gp.Asn15Lys
missense
Exon 2 of 23ENSP00000631397.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.024
DANN
Benign
0.89
DEOGEN2
Benign
0.021
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.41
N
PhyloP100
-1.0
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.14
N
REVEL
Benign
0.010
Sift
Benign
0.14
T
Sift4G
Benign
0.72
T
Polyphen
0.0040
B
Vest4
0.087
MutPred
0.32
Gain of sheet (P = 0.0061)
MVP
0.12
MPC
0.62
ClinPred
0.063
T
GERP RS
-2.8
Varity_R
0.027
gMVP
0.10
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs144039014; hg19: chr4-37903761; API