NM_014547.5:c.-75+881A>G

Variant names:

• chr15-51830717-A-G
• rs2014638
• NM_014547.5:c.-75+881A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMOD3	NM_014547.5	c.-75+881A>G		intron_variant	Intron 1 of 9	ENST00000308580.12	NP_055362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMOD3	ENST00000308580.12	c.-75+881A>G		intron_variant	Intron 1 of 9	1	NM_014547.5	ENSP00000308753.7
TMOD3	ENST00000558455.1	c.-140+881A>G		intron_variant	Intron 1 of 2	3		ENSP00000454161.1

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

African (AFR) AF: 0.463 AC: 19178 AN: 41448

American (AMR) AF: 0.529 AC: 8081 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1407 AN: 3466

East Asian (EAS) AF: 0.367 AC: 1899 AN: 5174

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4826

European-Finnish (FIN) AF: 0.453 AC: 4774 AN: 10530

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31508 AN: 67956

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.469 Hom.: 46010

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
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2014638; hg19: chr15-52122914;