dbSNP rs2554309: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMOD3	NM_014547.5 link	c.406+142T>C		intron_variant	Intron 4 of 9	ENST00000308580.12	NP_055362.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TMOD3	ENST00000308580.12 link	c.406+142T>C	intron_variant	Intron 4 of 9	1	NM_014547.5	ENSP00000308753.7
TMOD3	ENST00000560549.5 link	n.-12+142T>C	intron_variant	Intron 2 of 11	1		ENSP00000454040.1
ENSG00000259201	ENST00000558142.1 link	n.352-135A>G	intron_variant	Intron 3 of 3	3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over