Genetic Variant TMOD3:c.406+142T>C (chr15-51887853-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014547.5(TMOD3):c.406+142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,013,978 control chromosomes in the GnomAD database, including 985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.051 ( 475 hom., cov: 32)

Exomes 𝑓: 0.015 ( 510 hom. )

Consequence

TMOD3
NM_014547.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

Publications

2 publications found

Variant links:

Genes affected

TMOD3 (HGNC:11873): (tropomodulin 3) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in actin filament organization; muscle contraction; and myofibril assembly. Predicted to act upstream of or within actin cytoskeleton organization; erythrocyte development; and positive regulation of mitotic cell cycle phase transition. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

TMOD3 links:

ENSG00000259201 (HGNC:):

ENSG00000259201 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014547.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD3	NM_014547.5	MANE Select	c.406+142T>C		intron	N/A	NP_055362.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMOD3	ENST00000308580.12	TSL:1 MANE Select	c.406+142T>C	intron	N/A	ENSP00000308753.7
TMOD3	ENST00000560549.5	TSL:1	n.-12+142T>C	intron	N/A	ENSP00000454040.1
ENSG00000259201	ENST00000558142.1	TSL:3	n.352-135A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0513

AC:

7807

AN:

152204

Hom.:

474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0859

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00588

Gnomad OTH

AF:

0.0535

GnomAD4 exome

AF:

0.0148

AC:

12726

AN:

861656

Hom.:

510

AF XY:

0.0143

AC XY:

6297

AN XY:

439752

show subpopulations

African (AFR)

AF:

0.136

AC:

2443

AN:

17898

American (AMR)

AF:

0.115

AC:

1997

AN:

17320

Ashkenazi Jewish (ASJ)

AF:

0.00654

AC:

121

AN:

18492

East Asian (EAS)

AF:

0.0987

AC:

3065

AN:

31060

South Asian (SAS)

AF:

0.0165

AC:

879

AN:

53218

European-Finnish (FIN)

AF:

0.00328

AC:

143

AN:

43542

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

4330

European-Non Finnish (NFE)

AF:

0.00486

AC:

3095

AN:

636554

Other (OTH)

AF:

0.0234

AC:

919

AN:

39242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

572

1143

1715

2286

2858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.0515

AC:

7840

AN:

152322

Hom.:

475

Cov.:

AF XY:

0.0508

AC XY:

3783

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.132

AC:

5494

AN:

41556

American (AMR)

AF:

0.0860

AC:

1316

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3470

East Asian (EAS)

AF:

0.0725

AC:

376

AN:

5188

South Asian (SAS)

AF:

0.0178

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00588

AC:

400

AN:

68034

Other (OTH)

AF:

0.0535

AC:

113

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

363

725

1088

1450

1813

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:

0.0366

Hom.:

Bravo

AF:

0.0637

Asia WGS

AF:

0.0610

AC:

214

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.3

(source)

DANN

Benign

0.41

PhyloP100

0.084

Mutation Taster

=100/0

polymorphism (auto)

(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

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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