22-30296364-A-G

Variant names:

• chr22-30296364-A-G
• rs929454
• NM_031937.3:c.418-521T>C

Variant summary

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

The NM_031937.3(TBC1D10A):​c.418-521T>C 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D10A NM_031937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

TBC1D10A (HGNC:23609): (TBC1 domain family member 10A) Enables PDZ domain binding activity. Involved in activation of cysteine-type endopeptidase activity and retrograde transport, endosome to Golgi. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000248751 (HGNC:):

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=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D10A	NM_031937.3	c.418-521T>C		intron_variant	Intron 3 of 8	ENST00000215790.12	NP_114143.1
TBC1D10A	NM_001204240.2	c.439-521T>C		intron_variant	Intron 3 of 8		NP_001191169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D10A	ENST00000215790.12	c.418-521T>C		intron_variant	Intron 3 of 8	1	NM_031937.3	ENSP00000215790.8
ENSG00000248751	ENST00000434291.5	c.40-521T>C		intron_variant	Intron 1 of 12	2		ENSP00000401535.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1558 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.57

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: rs929454; hg19: chr22-30692353;