Genetic Variant TBC1D10A:c.418-521T>A (chr22-30296364-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.13

Publications

10 publications found

Variant links:

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]

TBC1D10A links:

ENSG00000248751 (HGNC:):

ENSG00000248751 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.418-521T>A		intron_variant	Intron 3 of 8	ENST00000215790.12	NP_114143.1	Q9BXI6-1A7E244B7ZVY9
TBC1D10A	NM_001204240.2 link	c.439-521T>A		intron_variant	Intron 3 of 8		NP_001191169.1	Q9BXI6-2A7E244

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D10A	ENST00000215790.12 link	c.418-521T>A		intron_variant	Intron 3 of 8	1	NM_031937.3	ENSP00000215790.8		Q9BXI6-1
ENSG00000248751	ENST00000434291.5 link	c.40-521T>A		intron_variant	Intron 1 of 12	2		ENSP00000401535.1		H7C1Q1

Frequencies

GnomAD3 genomes

AF:

0.876

AC:

133195

AN:

152128

Hom.:

58670

Cov.:

show subpopulations

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.:

AF XY:

0.840

AC XY:

675

AN XY:

804

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.869

AC:

292

AN:

336

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.921

AC:

151

AN:

164

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.807

AC:

770

AN:

954

Other (OTH)

AF:

0.886

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.876

AC:

133311

AN:

152246

Hom.:

58729

Cov.:

AF XY:

0.881

AC XY:

65548

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.967

AC:

40196

AN:

41564

American (AMR)

AF:

0.871

AC:

13329

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.893

AC:

3097

AN:

3470

East Asian (EAS)

AF:

0.904

AC:

4669

AN:

5162

South Asian (SAS)

AF:

0.915

AC:

4412

AN:

4822

European-Finnish (FIN)

AF:

0.888

AC:

9413

AN:

10604

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.814

AC:

55395

AN:

68012

Other (OTH)

AF:

0.881

AC:

1858

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

836

1672

2507

3343

4179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.29

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over