Genetic Variant TRIP13:c.92+7C>T (chr5-893097-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_004237.4(TRIP13):c.92+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,583,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TRIP13
NM_004237.4 splice_region, intron

Scores

Splicing: ADA: 0.0003104

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.21

Publications

0 publications found

Variant links:

Genes affected

TRIP13 (HGNC:12307): (thyroid hormone receptor interactor 13) This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer. [provided by RefSeq, Oct 2009]

TRIP13 Gene-Disease associations (from GenCC):

mosaic variegated aneuploidy syndrome 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
oocyte maturation defect 9
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
female infertility due to oocyte meiotic arrest
Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
kidney Wilms tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
mosaic variegated aneuploidy syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRIP13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-893097-C-T is Benign according to our data. Variant chr5-893097-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3358469.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004237.4. 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
	TRIP13	NM_004237.4	MANE Select	c.92+7C>T		splice_region intron	N/A	NP_004228.1	Q15645-1
	TRIP13	NM_001166260.2		c.92+7C>T		splice_region intron	N/A	NP_001159732.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRIP13	ENST00000166345.8	TSL:1 MANE Select	c.92+7C>T	splice_region intron	N/A	ENSP00000166345.3	Q15645-1
TRIP13	ENST00000512024.5	TSL:1	n.207+7C>T	splice_region intron	N/A
TRIP13	ENST00000891004.1		c.92+7C>T	splice_region intron	N/A	ENSP00000561063.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000205

AC:

AN:

194988

AF XY:

0.00000934

show subpopulations

Gnomad AFR exome

AF:

0.000260

Gnomad AMR exome

AF:

0.0000332

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000161

AC:

AN:

1431170

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

710278

show subpopulations

African (AFR)

AF:

0.000303

AC:

AN:

33054

American (AMR)

AF:

0.0000240

AC:

AN:

41752

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25562

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38748

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41116

Middle Eastern (MID)

AF:

0.000353

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.00000544

AC:

AN:

1103260

Other (OTH)

AF:

0.0000336

AC:

AN:

59520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

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:

0.00

Hom.:

Bravo

AF:

0.0000491

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

TRIP13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.0

(source)

DANN

Benign

0.92

PhyloP100

-1.2

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.0

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