rs16935797

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-8099753-T-C
• chr11-8099753-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUB	NM_177972.3	c.1117-750T>C		intron_variant	Intron 9 of 11	ENST00000299506.3	NP_813977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUB	ENST00000299506.3	c.1117-750T>C		intron_variant	Intron 9 of 11	1	NM_177972.3	ENSP00000299506.3
TUB	ENST00000305253.8	c.1282-750T>C		intron_variant	Intron 10 of 12	1		ENSP00000305426.4
TUB	ENST00000534099.5	c.1135-750T>C		intron_variant	Intron 9 of 11	2		ENSP00000434400.1

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.0828

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.102

Alfa AF: 0.130 Hom.: 807

Bravo AF: 0.146

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.085
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs16935797; hg19: chr11-8121300;