22-30318695-A-C

Variant names:

• chr22-30318695-A-C
• rs740219
• NM_031937.3:c.209+7978T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031937.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10A	NM_031937.3	MANE Select	c.209+7978T>G		intron	N/A	NP_114143.1
	TBC1D10A	NM_001204240.2		c.209+7978T>G		intron	N/A	NP_001191169.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10A	ENST00000215790.12	TSL:1 MANE Select	c.209+7978T>G		intron	N/A	ENSP00000215790.8
	TBC1D10A	ENST00000433426.5	TSL:5	n.-29T>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000400620.1
	TBC1D10A	ENST00000433426.5	TSL:5	n.-29T>G		5_prime_UTR	Exon 1 of 10	ENSP00000400620.1

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

GnomAD2 exomes AF: 0.864 AC: 126890 AN: 146784 AF XY: 0.867

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 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

African (AFR) AF: 0.970 AC: 8374 AN: 8632

American (AMR) AF: 0.851 AC: 23214 AN: 27286

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 9596 AN: 10790

East Asian (EAS) AF: 0.905 AC: 8335 AN: 9214

South Asian (SAS) AF: 0.919 AC: 54904 AN: 59744

European-Finnish (FIN) AF: 0.878 AC: 23755 AN: 27062

Middle Eastern (MID) AF: 0.943 AC: 2625 AN: 2784

European-Non Finnish (NFE) AF: 0.814 AC: 129450 AN: 159024

Other (OTH) AF: 0.861 AC: 12336 AN: 14326

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

African (AFR) AF: 0.967 AC: 40185 AN: 41558

American (AMR) AF: 0.873 AC: 13350 AN: 15292

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

East Asian (EAS) AF: 0.905 AC: 4674 AN: 5164

South Asian (SAS) AF: 0.915 AC: 4415 AN: 4824

European-Finnish (FIN) AF: 0.889 AC: 9427 AN: 10608

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

European-Non Finnish (NFE) AF: 0.814 AC: 55337 AN: 68014

Other (OTH) AF: 0.879 AC: 1859 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.2
DANN	Benign	0.66
PhyloP100		-0.26
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: rs740219; hg19: chr22-30714684;