chr22-30315454-A-G

Variant names:

• chr22-30315454-A-G
• rs4820831
• NM_031937.3:c.210-10824T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031937.3(TBC1D10A):​c.210-10824T>C 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 152,180 control chromosomes in the GnomAD database, including 58,642 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 (58642 hom., cov: 31)
• Consequence: TBC1D10A NM_031937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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.210-10824T>C		intron_variant	Intron 1 of 8	ENST00000215790.12	NP_114143.1
TBC1D10A	NM_001204240.2	c.210-10803T>C		intron_variant	Intron 1 of 8		NP_001191169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D10A	ENST00000215790.12	c.210-10824T>C		intron_variant	Intron 1 of 8	1	NM_031937.3	ENSP00000215790.8

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133065 AN: 152062 Hom.: 58583 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.875 AC: 133181 AN: 152180 Hom.: 58642 Cov.: 31 AF XY: 0.880 AC XY: 65468 AN XY: 74388

African (AFR) AF: 0.967 AC: 40164 AN: 41536

American (AMR) AF: 0.872 AC: 13327 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3098 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4679 AN: 5170

South Asian (SAS) AF: 0.915 AC: 4406 AN: 4816

European-Finnish (FIN) AF: 0.888 AC: 9404 AN: 10592

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55301 AN: 67984

Other (OTH) AF: 0.879 AC: 1861 AN: 2116

Alfa AF: 0.842 Hom.: 6325

Bravo AF: 0.875

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	-0.96
CADD	Benign	0.49
DANN	Benign	0.30
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4820831; hg19: chr22-30711443;