chr6-121333450-A-T

Position:

• chr6-121333450-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152730.6(TBC1D32):​c.155+826T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: TBC1D32 NM_152730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

Genes affected

TBC1D32 (HGNC:21485): (TBC1 domain family member 32) This gene encodes a TBC-domain containing protein. Studies of a similar protein in mouse and zebrafish suggest that the encoded protein is involved in sonic hedgehog signaling, and that it interacts with and stabilizes cell cycle-related kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D32	NM_152730.6	c.155+826T>A		intron_variant		ENST00000398212.7	NP_689943.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D32	ENST00000398212.7	c.155+826T>A		intron_variant		5	NM_152730.6	ENSP00000381270
TBC1D32	ENST00000275159.11	c.155+826T>A		intron_variant		5		ENSP00000275159	P1
TBC1D32	ENST00000422369.1	c.155+826T>A		intron_variant		3		ENSP00000397993
TBC1D32	ENST00000464622.5	c.155+826T>A		intron_variant, NMD_transcript_variant		2		ENSP00000428839

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.84

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: rs9320808; hg19: chr6-121654596;