rs58983546

Variant names:

• chr4-38053116-C-G
• rs58983546
• NM_001396959.1:c.2083C>G
• TBC1D1 p.Arg695Gly

Your query was ambiguous. Multiple possible variants found:

• chr4-38053116-C-G
• chr4-38053116-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001396959.1(TBC1D1):​c.2083C>G​(p.Arg695Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000334 in 1,497,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: TBC1D1 NM_001396959.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09
• Publications: 11 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2906878).

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.2083C>G	p.Arg695Gly	missense	Exon 13 of 22	NP_001383888.1	A0A8V8TNS9
	TBC1D1	NM_001253912.2		c.2083C>G	p.Arg695Gly	missense	Exon 13 of 21	NP_001240841.1	Q86TI0-2
	TBC1D1	NM_015173.4		c.1911-1083C>G		intron	N/A	NP_055988.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D1	ENST00000698857.1	MANE Select	c.2083C>G	p.Arg695Gly	missense	Exon 13 of 22	ENSP00000513987.1	A0A8V8TNS9
	TBC1D1	ENST00000261439.9	TSL:1	c.1911-1083C>G		intron	N/A	ENSP00000261439.4	Q86TI0-1
	TBC1D1	ENST00000961338.1		c.2083C>G	p.Arg695Gly	missense	Exon 13 of 23	ENSP00000631397.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151942 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1345596 Hom.: 0 Cov.: 30 AF XY: 0.00000151 AC XY: 1 AN XY: 662446

African (AFR) AF: 0.00 AC: 0 AN: 28710

American (AMR) AF: 0.00 AC: 0 AN: 26022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23656

East Asian (EAS) AF: 0.00 AC: 0 AN: 33198

South Asian (SAS) AF: 0.00 AC: 0 AN: 69042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 0.00000378 AC: 4 AN: 1056832

Other (OTH) AF: 0.00 AC: 0 AN: 55504

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151942 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74180

African (AFR) AF: 0.0000242 AC: 1 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.2	T
PhyloP100		6.1
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.21
Sift	Benign	0.13	T
Sift4G	Benign	0.32	T
Mutation Taster		=81/19	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: rs58983546;

hg19: chr4-38054737;