dbSNP rs3748172: TNC:p.Ala1055Ala (chr9-115073652-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002160.4(TNC):c.3165C>T(p.Ala1055Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,102 control chromosomes in the GnomAD database, including 852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 114 hom., cov: 32)

Exomes 𝑓: 0.012 ( 738 hom. )

Consequence

TNC
NM_002160.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -5.43

Publications

5 publications found

Variant links:

Genes affected

TNC (HGNC:5318): (tenascin C) This gene encodes an extracellular matrix protein with a spatially and temporally restricted tissue distribution. This protein is homohexameric with disulfide-linked subunits, and contains multiple EGF-like and fibronectin type-III domains. It is implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity, and neuronal regeneration. [provided by RefSeq, Jul 2011]

TNC links:

DELEC1 (HGNC:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

DELEC1 links:

LOC124902256 (HGNC:):

LOC124902256 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-115073652-G-A is Benign according to our data. Variant chr9-115073652-G-A is described in ClinVar as Benign. ClinVar VariationId is 586834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNC	NM_002160.4	MANE Select	c.3165C>T	p.Ala1055Ala	synonymous	Exon 10 of 28	NP_002151.2
TNC	NM_001439065.1		c.3165C>T	p.Ala1055Ala	synonymous	Exon 10 of 30	NP_001425994.1
TNC	NM_001439066.1		c.3165C>T	p.Ala1055Ala	synonymous	Exon 11 of 31	NP_001425995.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNC	ENST00000350763.9	TSL:1 MANE Select	c.3165C>T	p.Ala1055Ala	synonymous	Exon 10 of 28	ENSP00000265131.4
TNC	ENST00000423613.6	TSL:1	c.3165C>T	p.Ala1055Ala	synonymous	Exon 10 of 25	ENSP00000411406.2
TNC	ENST00000542877.6	TSL:1	c.3165C>T	p.Ala1055Ala	synonymous	Exon 10 of 24	ENSP00000442242.1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2479

AN:

152116

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0792

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0626

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00218

Gnomad OTH

AF:

0.0235

GnomAD2 exomes

AF:

0.0333

AC:

8344

AN:

250572

AF XY:

0.0311

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

AF:

0.0117

AC:

17166

AN:

1461868

Hom.:

738

Cov.:

AF XY:

0.0127

AC XY:

9215

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

33478

American (AMR)

AF:

0.114

AC:

5107

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26130

East Asian (EAS)

AF:

0.0964

AC:

3828

AN:

39698

South Asian (SAS)

AF:

0.0559

AC:

4822

AN:

86258

European-Finnish (FIN)

AF:

0.00848

AC:

453

AN:

53420

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00179

AC:

1988

AN:

1112000

Other (OTH)

AF:

0.0142

AC:

857

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

923

1846

2769

3692

4615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

240

480

720

960

1200

<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:

0.0164

AC:

2490

AN:

152234

Hom.:

114

Cov.:

AF XY:

0.0198

AC XY:

1472

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00253

AC:

105

AN:

41532

American (AMR)

AF:

0.0796

AC:

1217

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

554

AN:

5178

South Asian (SAS)

AF:

0.0633

AC:

305

AN:

4822

European-Finnish (FIN)

AF:

0.0105

AC:

111

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00216

AC:

147

AN:

68012

Other (OTH)

AF:

0.0242

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

227

340

454

567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00922

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Aug 10, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal dominant nonsyndromic hearing loss 56

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.38

(source)

DANN

Benign

0.42

PhyloP100

-5.4

Mutation Taster

=94/6

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over