rs2279027

Variant names:

• chr4-37902135-T-A
• rs2279027
• NM_001396959.1:c.40T>A
• TBC1D1 p.Ser14Thr

Your query was ambiguous. Multiple possible variants found:

• chr4-37902135-T-A
• chr4-37902135-T-C
• chr4-37902135-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001396959.1(TBC1D1):​c.40T>A​(p.Ser14Thr) 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.

• Frequency: Genomes: not found (cov: 29)
• Consequence: TBC1D1 NM_001396959.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 37 publications found

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

ACMG classification

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=0.087320656).

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	NM_001396959.1	MANE Select	c.40T>A	p.Ser14Thr	missense	Exon 2 of 22	NP_001383888.1	A0A8V8TNS9
	TBC1D1	NM_015173.4		c.40T>A	p.Ser14Thr	missense	Exon 2 of 20	NP_055988.2
	TBC1D1	NM_001253912.2		c.40T>A	p.Ser14Thr	missense	Exon 2 of 21	NP_001240841.1	Q86TI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	ENST00000698857.1	MANE Select	c.40T>A	p.Ser14Thr	missense	Exon 2 of 22	ENSP00000513987.1	A0A8V8TNS9
	TBC1D1	ENST00000261439.9	TSL:1	c.40T>A	p.Ser14Thr	missense	Exon 2 of 20	ENSP00000261439.4	Q86TI0-1
	TBC1D1	ENST00000961338.1		c.40T>A	p.Ser14Thr	missense	Exon 2 of 23	ENSP00000631397.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.25
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.074
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.24	T
Varity_R		0.042
gMVP		0.30
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2279027;

hg19: chr4-37903756;