chr22-30296364-A-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031937.3(TBC1D10A):​c.418-521T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 153,804 control chromosomes in the GnomAD database, including 59,269 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 0.88 (58729 hom., cov: 32)
  • Exomes 𝑓: 0.84 (540 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D10A	NM_031937.3	c.418-521T>A		intron_variant	Intron 3 of 8	ENST00000215790.12	NP_114143.1
TBC1D10A	NM_001204240.2	c.439-521T>A		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>A		intron_variant	Intron 3 of 8	1	NM_031937.3	ENSP00000215790.8
ENSG00000248751	ENST00000434291.5	c.40-521T>A		intron_variant	Intron 1 of 12	2		ENSP00000401535.1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133195 AN: 152128 Hom.: 58670 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.879

GnomAD4 exome AF: 0.837 AC: 1304 AN: 1558 Hom.: 540 Cov.: 0 AF XY: 0.840 AC XY: 675 AN XY: 804

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.869

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.876 AC: 133311 AN: 152246 Hom.: 58729 Cov.: 32 AF XY: 0.881 AC XY: 65548 AN XY: 74434

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.881

Alfa AF: 0.847 Hom.: 6828

Bravo AF: 0.875

Asia WGS AF: 0.921 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;