dbSNP rs200948850: TCP10L3:n.1063C>T (chr6-167373273-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The ENST00000397829.9(TCP10L3):n.1063C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 150,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 41)

Exomes 𝑓: 0.00045 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

TCP10L3
ENST00000397829.9 non_coding_transcript_exon

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.0440

Publications

1 publications found

Variant links:

Genes affected

TCP10L3 (HGNC:):

TCP10L3 links:

TCP10L3 (HGNC:11656): (t-complex 10 like 3 (pseudogene))

TCP10L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

BayesDel_addAF computational evidence supports a deleterious effect, 0.262

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397829.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
TCP10L3	NR_163193.1	n.943C>T	non_coding_transcript_exon	Exon 6 of 6
TCP10L3	NR_163194.1	n.1089C>T	non_coding_transcript_exon	Exon 8 of 8
TCP10L3	NR_163195.1	n.1016C>T	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
TCP10L3	ENST00000397829.9	TSL:1	n.1063C>T	non_coding_transcript_exon	Exon 8 of 8
TCP10L3	ENST00000514083.1	TSL:1	n.1539C>T	non_coding_transcript_exon	Exon 2 of 2
TCP10L3	ENST00000463894.7	TSL:2	n.3324C>T	non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.00340

AC:

513

AN:

150698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00278

Gnomad ASJ

AF:

0.00321

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00227

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.00674

GnomAD2 exomes

AF:

0.000440

AC:

109

AN:

247698

AF XY:

0.000432

show subpopulations

Gnomad AFR exome

AF:

0.00505

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000449

AC:

651

AN:

1450478

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

333

AN XY:

721610

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00500

AC:

167

AN:

33420

American (AMR)

AF:

0.000338

AC:

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.000618

AC:

AN:

25900

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000697

AC:

AN:

86102

European-Finnish (FIN)

AF:

0.000453

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.000703

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.000336

AC:

370

AN:

1102408

Other (OTH)

AF:

0.000818

AC:

AN:

59888

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.288

Heterozygous variant carriers

161

242

322

403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00340

AC:

513

AN:

150816

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

258

AN XY:

73806

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00415

AC:

172

AN:

41470

American (AMR)

AF:

0.00277

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00321

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00227

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00366

AC:

245

AN:

66900

Other (OTH)

AF:

0.00667

AC:

AN:

2100

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.299

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00360

Hom.:

ESP6500AA

AF:

0.00347

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00222

AC:

268

ClinVar

ClinVar submissions as Germline

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

7.7

(source)

DANN

Benign

0.93

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.051

PhyloP100

0.044

Vest4

0.049

GERP RS

0.93

Mutation Taster

=199/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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