17-39665517-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003673.4(TCAP):c.110+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 1,565,592 control chromosomes in the GnomAD database, including 2,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 256 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2511 hom. )

Consequence

TCAP
NM_003673.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.843

Publications

6 publications found

Variant links:

Genes affected

TCAP (HGNC:11610): (titin-cap) Sarcomere assembly is regulated by the muscle protein titin. Titin is a giant elastic protein with kinase activity that extends half the length of a sarcomere. It serves as a scaffold to which myofibrils and other muscle related proteins are attached. This gene encodes a protein found in striated and cardiac muscle that binds to the titin Z1-Z2 domains and is a substrate of titin kinase, interactions thought to be critical to sarcomere assembly. Mutations in this gene are associated with limb-girdle muscular dystrophy type 2G. [provided by RefSeq, Jul 2008]

TCAP Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 25
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal recessive limb-girdle muscular dystrophy type 2G
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

TCAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-39665517-C-T is Benign according to our data. Variant chr17-39665517-C-T is described in ClinVar as Benign. ClinVar VariationId is 259120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCAP	NM_003673.4 link	c.110+48C>T		intron_variant	Intron 1 of 1	ENST00000309889.3	NP_003664.1	O15273A2TDC0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCAP	ENST00000309889.3 link	c.110+48C>T		intron_variant	Intron 1 of 1	1	NM_003673.4	ENSP00000312624.2		O15273
TCAP	ENST00000578283.1 link	c.110+48C>T		intron_variant	Intron 1 of 2	5		ENSP00000462787.1		J3KT40

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7733

AN:

152064

Hom.:

255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0432

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0579

Gnomad OTH

AF:

0.0407

GnomAD2 exomes

AF:

0.0390

AC:

9537

AN:

244774

AF XY:

0.0369

show subpopulations

Gnomad AFR exome

AF:

0.0713

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0396

GnomAD4 exome

AF:

0.0543

AC:

76805

AN:

1413410

Hom.:

2511

Cov.:

AF XY:

0.0522

AC XY:

36848

AN XY:

705802

show subpopulations

African (AFR)

AF:

0.0707

AC:

2300

AN:

32546

American (AMR)

AF:

0.0202

AC:

895

AN:

44382

Ashkenazi Jewish (ASJ)

AF:

0.00908

AC:

234

AN:

25770

East Asian (EAS)

AF:

0.0000761

AC:

AN:

39426

South Asian (SAS)

AF:

0.00584

AC:

498

AN:

85276

European-Finnish (FIN)

AF:

0.0495

AC:

2575

AN:

52016

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

4730

European-Non Finnish (NFE)

AF:

0.0631

AC:

67522

AN:

1070652

Other (OTH)

AF:

0.0465

AC:

2728

AN:

58612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3803

7607

11410

15214

19017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2494

4988

7482

9976

12470

<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:

0.0509

AC:

7749

AN:

152182

Hom.:

256

Cov.:

AF XY:

0.0479

AC XY:

3562

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0674

AC:

2801

AN:

41530

American (AMR)

AF:

0.0240

AC:

367

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.000582

AC:

AN:

5158

South Asian (SAS)

AF:

0.00435

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0432

AC:

458

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0580

AC:

3939

AN:

67966

Other (OTH)

AF:

0.0402

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

369

739

1108

1478

1847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0492

Hom.:

300

Bravo

AF:

0.0513

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.95

(source)

DANN

Benign

0.70

PhyloP100

-0.84

PromoterAI

-0.055

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over