rs740219

chr22-30318695-A-Cchr22-30318695-A-Gchr22-30318695-A-T

Variant summary

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

The NM_031937.3(TBC1D10A):c.209+7978T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 471,112 control chromosomes in the GnomAD database, including 175,689 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 (58707 hom., cov: 32)
  • Exomes 𝑓: 0.85 (116982 hom.)
• Consequence: TBC1D10A NM_031937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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/exons	MANE	UniProt
TBC1D10A	NM_031937.3	c.209+7978T>G		intron_variant		ENST00000215790.12
TBC1D10A	NM_001204240.2	c.209+7978T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D10A	ENST00000215790.12	c.209+7978T>G		intron_variant		1	NM_031937.3	P1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133169 AN: 152132 Hom.: 58648 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.878

GnomAD3 exomes AF: 0.864 AC: 126890 AN: 146784 Hom.: 54978 AF XY: 0.867 AC XY: 68615 AN XY: 79156

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.852

Gnomad ASJ exome AF: 0.890

Gnomad EAS exome AF: 0.906

Gnomad SAS exome AF: 0.919

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.817

Gnomad OTH exome AF: 0.852

GnomAD4 exome AF: 0.855 AC: 272589 AN: 318862 Hom.: 116982 Cov.: 0 AF XY: 0.860 AC XY: 154976 AN XY: 180154

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.851

Gnomad4 ASJ exome AF: 0.889

Gnomad4 EAS exome AF: 0.905

Gnomad4 SAS exome AF: 0.919

Gnomad4 FIN exome AF: 0.878

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.861

GnomAD4 genome AF: 0.875 AC: 133285 AN: 152250 Hom.: 58707 Cov.: 32 AF XY: 0.880 AC XY: 65545 AN XY: 74450

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.879

Alfa AF: 0.834 Hom.: 6182

Bravo AF: 0.876

Asia WGS AF: 0.923 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	5.2
Dann	Benign	0.66

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: rs740219; hg19: chr22-30714684;