NM_001396959.1:c.45C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001396959.1(TBC1D1):​c.45C>T​(p.Asn15Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,611,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: TBC1D1 NM_001396959.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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):

• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 4-37902140-C-T is Benign according to our data. Variant chr4-37902140-C-T is described in ClinVar as Benign. ClinVar VariationId is 787799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 261 AD gene.

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.45C>T	p.Asn15Asn	synonymous	Exon 2 of 22	NP_001383888.1	A0A8V8TNS9
	TBC1D1	NM_015173.4		c.45C>T	p.Asn15Asn	synonymous	Exon 2 of 20	NP_055988.2
	TBC1D1	NM_001253912.2		c.45C>T	p.Asn15Asn	synonymous	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.45C>T	p.Asn15Asn	synonymous	Exon 2 of 22	ENSP00000513987.1	A0A8V8TNS9
	TBC1D1	ENST00000261439.9	TSL:1	c.45C>T	p.Asn15Asn	synonymous	Exon 2 of 20	ENSP00000261439.4	Q86TI0-1
	TBC1D1	ENST00000961338.1		c.45C>T	p.Asn15Asn	synonymous	Exon 2 of 23	ENSP00000631397.1

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 259 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

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: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000426 AC: 106 AN: 248696 AF XY: 0.000320

Gnomad AFR exome AF: 0.00592

Gnomad AMR exome AF: 0.000177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000184 AC: 268 AN: 1459672 Hom.: 1 Cov.: 36 AF XY: 0.000169 AC XY: 123 AN XY: 726304

African (AFR) AF: 0.00636 AC: 212 AN: 33328

American (AMR) AF: 0.000341 AC: 15 AN: 44022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111180

Other (OTH) AF: 0.000448 AC: 27 AN: 60236

GnomAD4 genome AF: 0.00171 AC: 261 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.00167 AC XY: 124 AN XY: 74392

African (AFR) AF: 0.00552 AC: 229 AN: 41502

American (AMR) AF: 0.00170 AC: 26 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.000897 Hom.: 0

Bravo AF: 0.00187

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	TBC1D1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.58
DANN	Benign	0.55
PhyloP100		-1.0

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

Other links and lift over

dbSNP: rs144039014; hg19: chr4-37903761; COSMIC: COSV54725972;