Variant 4-140624222-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_015130.3(TBC1D9):c.2975-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,611,432 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 16 hom. )

Consequence

TBC1D9
NM_015130.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007525

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.11

Variant links:

Genes affected

TBC1D9 (HGNC:21710): (TBC1 domain family member 9) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 4-140624222-A-G is Benign according to our data. Variant chr4-140624222-A-G is described in ClinVar as [Benign]. Clinvar id is 767977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1535/152286) while in subpopulation AFR AF= 0.0345 (1434/41554). AF 95% confidence interval is 0.033. There are 24 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D9	NM_015130.3 linkuse as main transcript	c.2975-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000442267.3	NP_055945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D9	ENST00000442267.3 linkuse as main transcript	c.2975-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015130.3	ENSP00000411197	P1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1532

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00282

AC:

687

AN:

243664

Hom.:

AF XY:

0.00201

AC XY:

265

AN XY:

132104

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00902

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000400

Gnomad OTH exome

AF:

0.00218

GnomAD4 exome

AF:

0.00123

AC:

1788

AN:

1459146

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

817

AN XY:

725556

show subpopulations

Gnomad4 AFR exome

AF:

0.0348

Gnomad4 AMR exome

AF:

0.00194

Gnomad4 ASJ exome

AF:

0.00829

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000934

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.0101

AC:

1535

AN:

152286

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

736

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00587

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.7

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000075

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over