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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10A	NM_031937.3	MANE Select	c.418-521T>A		intron	N/A	NP_114143.1	Q9BXI6-1
	TBC1D10A	NM_001204240.2		c.439-521T>A		intron	N/A	NP_001191169.1	Q9BXI6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBC1D10A	ENST00000215790.12	TSL:1 MANE Select	c.418-521T>A	intron	N/A	ENSP00000215790.8	Q9BXI6-1
ENSG00000248751	ENST00000434291.5	TSL:2	c.40-521T>A	intron	N/A	ENSP00000401535.1	H7C1Q1
TBC1D10A	ENST00000962332.1		c.418-521T>A	intron	N/A	ENSP00000632391.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over