rs2554309

Positions:

• chr15-51887853-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TMOD3	NM_014547.5	c.406+142T>C		intron_variant		ENST00000308580.12	NP_055362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD3	ENST00000308580.12	c.406+142T>C		intron_variant		1	NM_014547.5	ENSP00000308753	P1
TMOD3	ENST00000560549.5	c.-12+142T>C		intron_variant, NMD_transcript_variant		1		ENSP00000454040
	ENST00000558142.1	n.352-135A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7807 AN: 152204 Hom.: 474 Cov.: 32

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

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.00654

Gnomad4 EAS exome AF: 0.0987

Gnomad4 SAS exome AF: 0.0165

Gnomad4 FIN exome AF: 0.00328

Gnomad4 NFE exome AF: 0.00486

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0515 AC: 7840 AN: 152322 Hom.: 475 Cov.: 32 AF XY: 0.0508 AC XY: 3783 AN XY: 74490

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00588

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0331 Hom.: 49

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
DANN	Benign	0.41

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: rs2554309; hg19: chr15-52180050; COSMIC: COSV57944511; COSMIC: COSV57944511;