rs144039014

Variant names:

• chr4-37902140-C-G
• rs144039014
• NM_001396959.1:c.45C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-37902140-C-G
• chr4-37902140-C-T

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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 0 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):

• 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=0.10831636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.45C>G	p.Asn15Lys	missense_variant	Exon 2 of 22	ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.45C>G	p.Asn15Lys	missense_variant	Exon 2 of 22		NM_001396959.1	ENSP00000513987.1
TBC1D1	ENST00000261439.9	c.45C>G	p.Asn15Lys	missense_variant	Exon 2 of 20	1		ENSP00000261439.4
TBC1D1	ENST00000508802.5	c.45C>G	p.Asn15Lys	missense_variant	Exon 2 of 21	2		ENSP00000423651.1
TBC1D1	ENST00000402522.1	c.45C>G	p.Asn15Lys	missense_variant	Exon 2 of 3	2		ENSP00000383994.1

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 v4.3

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;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.41	N;N;.
PhyloP100		-1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.14	N;N;N
REVEL	Benign	0.010
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0040	.;B;.
Vest4		0.087
MutPred		0.32		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);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

Other links and lift over

dbSNP: rs144039014; hg19: chr4-37903761;