rs10101626

Variant names:

• chr8-123142457-G-T
• rs10101626
• NM_145647.4:c.2835+1G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000287380.6(TBC1D31):​c.2835+1G>T variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.189 in 1,534,894 control chromosomes in the GnomAD database, including 28,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.20 (3251 hom., cov: 31)
  • Exomes 𝑓: 0.19 (24881 hom.)
• Consequence: TBC1D31 ENST00000287380.6 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60
• Publications: 23 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.06091846 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000287380.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D31	NM_145647.4	MANE Select	c.2835+1G>T		splice_donor intron	N/A	NP_663622.2
	TBC1D31	NM_001363149.1		c.2805+1G>T		splice_donor intron	N/A	NP_001350078.1
	TBC1D31	NM_001363150.1		c.2742+1G>T		splice_donor intron	N/A	NP_001350079.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D31	ENST00000287380.6	TSL:1 MANE Select	c.2835+1G>T		splice_donor intron	N/A	ENSP00000287380.1
	TBC1D31	ENST00000327098.9	TSL:1	c.2547+1556G>T		intron	N/A	ENSP00000312701.5
	TBC1D31	ENST00000522420.5	TSL:1	c.2520+1G>T		splice_donor intron	N/A	ENSP00000429334.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30898 AN: 150920 Hom.: 3244 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.193 AC: 36583 AN: 189302 AF XY: 0.194

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.188 AC: 259618 AN: 1383864 Hom.: 24881 Cov.: 29 AF XY: 0.188 AC XY: 129011 AN XY: 685516

African (AFR) AF: 0.247 AC: 7230 AN: 29248

American (AMR) AF: 0.167 AC: 4942 AN: 29550

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4733 AN: 22878

East Asian (EAS) AF: 0.206 AC: 7602 AN: 36976

South Asian (SAS) AF: 0.218 AC: 16124 AN: 73846

European-Finnish (FIN) AF: 0.169 AC: 8692 AN: 51562

Middle Eastern (MID) AF: 0.205 AC: 1106 AN: 5406

European-Non Finnish (NFE) AF: 0.184 AC: 198168 AN: 1077542

Other (OTH) AF: 0.194 AC: 11021 AN: 56856

GnomAD4 genome AF: 0.205 AC: 30922 AN: 151030 Hom.: 3251 Cov.: 31 AF XY: 0.204 AC XY: 15025 AN XY: 73778

African (AFR) AF: 0.248 AC: 10120 AN: 40852

American (AMR) AF: 0.185 AC: 2807 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3462

East Asian (EAS) AF: 0.205 AC: 1057 AN: 5164

South Asian (SAS) AF: 0.221 AC: 1062 AN: 4810

European-Finnish (FIN) AF: 0.160 AC: 1658 AN: 10350

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12955 AN: 67886

Other (OTH) AF: 0.190 AC: 397 AN: 2092

Alfa AF: 0.195 Hom.: 9174

Bravo AF: 0.208

TwinsUK AF: 0.201 AC: 746

ALSPAC AF: 0.191 AC: 736

ExAC AF: 0.195 AC: 23628

Asia WGS AF: 0.217 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		6.6
GERP RS		5.4
Mutation Taster		=76/24	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.87
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.99		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10101626; hg19: chr8-124154697; COSMIC: COSV54870185; COSMIC: COSV54870185;