8-123077179-C-T

Variant names:

• chr8-123077179-C-T
• rs747229872
• NM_145647.4:c.146C>T

Variant summary

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

The NM_145647.4(TBC1D31):​c.146C>T​(p.Ala49Val) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,460,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TBC1D31 NM_145647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.35
• Publications: 0 publications found

Genes affected

TBC1D31 (HGNC:30888): (TBC1 domain family member 31) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D31 Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145647.4. 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
	TBC1D31	NM_145647.4	MANE Select	c.146C>T	p.Ala49Val	missense	Exon 2 of 22	NP_663622.2	Q96DN5-1
	TBC1D31	NM_001363149.1		c.116C>T	p.Ala39Val	missense	Exon 2 of 22	NP_001350078.1
	TBC1D31	NM_001363150.1		c.146C>T	p.Ala49Val	missense	Exon 2 of 21	NP_001350079.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D31	ENST00000287380.6	TSL:1 MANE Select	c.146C>T	p.Ala49Val	missense	Exon 2 of 22	ENSP00000287380.1	Q96DN5-1
	TBC1D31	ENST00000327098.9	TSL:1	c.146C>T	p.Ala49Val	missense	Exon 2 of 20	ENSP00000312701.5	Q96DN5-3
	TBC1D31	ENST00000522420.5	TSL:1	c.-54C>T		5_prime_UTR	Exon 2 of 21	ENSP00000429334.1	E7ERK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000360 AC: 9 AN: 250142 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460650 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726644

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.000225 AC: 10 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111540

Other (OTH) AF: 0.0000497 AC: 3 AN: 60312

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.072	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.058	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.89
MutPred		0.56		Loss of catalytic residue at A49 (P = 0.0885)
MVP		0.85
MPC		0.33
ClinPred		0.50	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.62
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs747229872; hg19: chr8-124089419;