NM_001330348.2:c.3416_3418dupCTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBA1

The NM_001330348.2(TBC1D8):c.3416_3418dupCTT(p.Thr1139_Phe1140insSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,864 control chromosomes in the GnomAD database, including 1,370 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.053 ( 715 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 655 hom. )

Consequence

TBC1D8
NM_001330348.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250

Publications

3 publications found

Variant links:

Genes affected

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D8 links:

RPL31 (HGNC:10334): (ribosomal protein L31) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPL31 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

RPL31 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001330348.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 2-101007870-A-AAAG is Benign according to our data. Variant chr2-101007870-A-AAAG is described in ClinVar as Benign. ClinVar VariationId is 1248315.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D8	NM_001330348.2	MANE Select	c.3416_3418dupCTT	p.Thr1139_Phe1140insSer	conservative_inframe_insertion	Exon 20 of 20	NP_001317277.1	J3KQ40
TBC1D8	NM_001102426.3		c.3371_3373dupCTT	p.Thr1124_Phe1125insSer	conservative_inframe_insertion	Exon 20 of 20	NP_001095896.1	O95759-1
RPL31	NM_001098577.3		c.346+1800_346+1802dupAAG		intron	N/A	NP_001092047.1	P62899-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D8	ENST00000409318.2	TSL:5 MANE Select	c.3416_3418dupCTT	p.Thr1139_Phe1140insSer	conservative_inframe_insertion	Exon 20 of 20	ENSP00000386856.1	J3KQ40
TBC1D8	ENST00000376840.8	TSL:1	c.3371_3373dupCTT	p.Thr1124_Phe1125insSer	conservative_inframe_insertion	Exon 20 of 20	ENSP00000366036.4	O95759-1
TBC1D8	ENST00000870702.1		c.3425_3427dupCTT	p.Thr1142_Phe1143insSer	conservative_inframe_insertion	Exon 20 of 20	ENSP00000540761.1

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8056

AN:

152056

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0138

AC:

3437

AN:

249220

AF XY:

0.0102

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.00985

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000549

Gnomad OTH exome

AF:

0.00793

GnomAD4 exome

AF:

0.00571

AC:

8345

AN:

1461690

Hom.:

655

Cov.:

AF XY:

0.00496

AC XY:

3605

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.192

AC:

6441

AN:

33476

American (AMR)

AF:

0.0109

AC:

489

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000290

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000495

AC:

550

AN:

1111866

Other (OTH)

AF:

0.0123

AC:

744

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

415

830

1245

1660

2075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0532

AC:

8090

AN:

152174

Hom.:

715

Cov.:

AF XY:

0.0521

AC XY:

3874

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.185

AC:

7677

AN:

41448

American (AMR)

AF:

0.0196

AC:

299

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68020

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

338

677

1015

1354

1692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.00908

Hom.:

Bravo

AF:

0.0609

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.025

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

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