chr8-123142035-C-T

Variant names:

• chr8-123142035-C-T
• rs6984928
• NM_145647.4:c.2641-227C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145647.4(TBC1D31):​c.2641-227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,320 control chromosomes in the GnomAD database, including 10,047 homozygotes. 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 0.34 (10047 hom., cov: 28)
• Consequence: TBC1D31 NM_145647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

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.2641-227C>T		intron	N/A	NP_663622.2	Q96DN5-1
	TBC1D31	NM_001363149.1		c.2611-227C>T		intron	N/A	NP_001350078.1
	TBC1D31	NM_001363150.1		c.2548-227C>T		intron	N/A	NP_001350079.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D31	ENST00000287380.6	TSL:1 MANE Select	c.2641-227C>T		intron	N/A	ENSP00000287380.1	Q96DN5-1
	TBC1D31	ENST00000327098.9	TSL:1	c.2547+1134C>T		intron	N/A	ENSP00000312701.5	Q96DN5-3
	TBC1D31	ENST00000522420.5	TSL:1	c.2326-227C>T		intron	N/A	ENSP00000429334.1	E7ERK7

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52009 AN: 151202 Hom.: 10019 Cov.: 28

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 52079 AN: 151320 Hom.: 10047 Cov.: 28 AF XY: 0.340 AC XY: 25155 AN XY: 73910

African (AFR) AF: 0.525 AC: 21643 AN: 41190

American (AMR) AF: 0.272 AC: 4143 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3464

East Asian (EAS) AF: 0.203 AC: 1041 AN: 5116

South Asian (SAS) AF: 0.231 AC: 1104 AN: 4788

European-Finnish (FIN) AF: 0.299 AC: 3117 AN: 10442

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19265 AN: 67814

Other (OTH) AF: 0.302 AC: 634 AN: 2100

Alfa AF: 0.272 Hom.: 1007

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.76
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs6984928; hg19: chr8-124154275;