Variant 17-39665517-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-39665517-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
TCAP	NM_003673.4 link	c.110+48C>T		intron_variant		ENST00000309889.3	NP_003664.1	O15273A2TDC0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCAP	ENST00000309889.3 link	c.110+48C>T		intron_variant		1	NM_003673.4	ENSP00000312624.2		O15273
TCAP	ENST00000578283.1 link	c.110+48C>T		intron_variant		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

GnomAD3 exomes

AF:

0.0390

AC:

9537

AN:

244774

Hom.:

259

AF XY:

0.0369

AC XY:

4899

AN XY:

132876

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 SAS exome

AF:

0.00575

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

Gnomad4 AFR exome

AF:

0.0707

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.00908

Gnomad4 EAS exome

AF:

0.0000761

Gnomad4 SAS exome

AF:

0.00584

Gnomad4 FIN exome

AF:

0.0495

Gnomad4 NFE exome

AF:

0.0631

Gnomad4 OTH exome

AF:

0.0465

GnomAD4 genome

AF:

0.0509

AC:

7749

AN:

152182

Hom.:

256

Cov.:

AF XY:

0.0479

AC XY:

3562

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0674

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0432

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0473

Hom.:

220

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.95

DANN

Benign

0.70

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

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