rs2014638

Positions:

• chr15-51830717-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014547.5(TMOD3):​c.-75+881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,988 control chromosomes in the GnomAD database, including 16,516 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 0.46 (16516 hom., cov: 31)
• Consequence: TMOD3 NM_014547.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMOD3	NM_014547.5	c.-75+881A>G		intron_variant		ENST00000308580.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMOD3	ENST00000308580.12	c.-75+881A>G		intron_variant		1	NM_014547.5	P1
TMOD3	ENST00000558455.1	c.-140+881A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70170 AN: 151868 Hom.: 16483 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 70259 AN: 151988 Hom.: 16516 Cov.: 31 AF XY: 0.458 AC XY: 34030 AN XY: 74282

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.482

Alfa AF: 0.466 Hom.: 27237

Bravo AF: 0.474

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.017
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs2014638; hg19: chr15-52122914;