chr11-8099753-T-C

Variant names:

• chr11-8099753-T-C
• rs16935797
• NM_177972.3:c.1117-750T>C

Variant summary

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

The NM_177972.3(TUB):​c.1117-750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,172 control chromosomes in the GnomAD database, including 1,808 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 0.15 (1808 hom., cov: 33)
• Consequence: TUB NM_177972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 publications found

Genes affected

TUB (HGNC:12406): (TUB bipartite transcription factor) This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

RIC3 (HGNC:30338): (RIC3 acetylcholine receptor chaperone) This gene encodes a member of the resistance to inhibitors of cholinesterase 3-like family which functions as a chaperone of specific 5-hydroxytryptamine type 3 receptor and nicotinic acetylcholine receptor subtypes. The encoded protein influences the folding and assembly of these receptor subunits in the endoplasmic reticulum and expression on the cell surface. This protein contains an N-terminal transmembrane domain, a proline-rich spacer, and a cytosolic C-terminal coiled-coil domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

RIC3 Gene-Disease associations (from GenCC):

• Parkinson disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• movement disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177972.3. 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
	TUB	NM_177972.3	MANE Select	c.1117-750T>C		intron	N/A	NP_813977.1	P50607-1
	TUB	NM_003320.5		c.1282-750T>C		intron	N/A	NP_003311.2
	TUB	NM_001440538.1		c.1135-750T>C		intron	N/A	NP_001427467.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUB	ENST00000299506.3	TSL:1 MANE Select	c.1117-750T>C		intron	N/A	ENSP00000299506.3	P50607-1
	TUB	ENST00000305253.8	TSL:1	c.1282-750T>C		intron	N/A	ENSP00000305426.4	P50607-2
	TUB	ENST00000534099.5	TSL:2	c.1135-750T>C		intron	N/A	ENSP00000434400.1	E9PQR4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22534 AN: 152054 Hom.: 1803 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.148 AC: 22563 AN: 152172 Hom.: 1808 Cov.: 33 AF XY: 0.148 AC XY: 11029 AN XY: 74394

African (AFR) AF: 0.179 AC: 7426 AN: 41504

American (AMR) AF: 0.110 AC: 1687 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3468

East Asian (EAS) AF: 0.0828 AC: 428 AN: 5170

South Asian (SAS) AF: 0.174 AC: 838 AN: 4826

European-Finnish (FIN) AF: 0.168 AC: 1778 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9620 AN: 68002

Other (OTH) AF: 0.102 AC: 216 AN: 2112

Alfa AF: 0.138 Hom.: 1359

Bravo AF: 0.146

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.085
DANN	Benign	0.79
PhyloP100		-1.2
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: rs16935797; hg19: chr11-8121300;