4-37902135-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001396959.1(TBC1D1):​c.40T>G​(p.Ser14Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Consequence

TBC1D1
NM_001396959.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057149738).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBC1D1NM_001396959.1 linkuse as main transcriptc.40T>G p.Ser14Ala missense_variant 2/22 ENST00000698857.1 NP_001383888.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBC1D1ENST00000698857.1 linkuse as main transcriptc.40T>G p.Ser14Ala missense_variant 2/22 NM_001396959.1 ENSP00000513987 A2
TBC1D1ENST00000261439.9 linkuse as main transcriptc.40T>G p.Ser14Ala missense_variant 2/201 ENSP00000261439 P2Q86TI0-1
TBC1D1ENST00000508802.5 linkuse as main transcriptc.40T>G p.Ser14Ala missense_variant 2/212 ENSP00000423651 Q86TI0-2
TBC1D1ENST00000402522.1 linkuse as main transcriptc.40T>G p.Ser14Ala missense_variant 2/32 ENSP00000383994

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
61
GnomAD4 genome
Cov.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
14
DANN
Benign
0.91
DEOGEN2
Benign
0.023
.;T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.55
T;T;T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.057
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.1
N;N;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.010
N;N;N
REVEL
Benign
0.087
Sift
Benign
0.27
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.071
MutPred
0.39
Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP
0.20
MPC
0.43
ClinPred
0.17
T
GERP RS
4.9
Varity_R
0.035
gMVP
0.20

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: rs2279027; hg19: chr4-37903756; API