rs10519326

Positions:

• chr15-51872923-C-T

Variant summary

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

The NM_014547.5(TMOD3):​c.283+3550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,298 control chromosomes in the GnomAD database, including 85 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 0.015 (85 hom., cov: 32)
• Consequence: TMOD3 NM_014547.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMOD3	NM_014547.5	c.283+3550C>T		intron_variant		ENST00000308580.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMOD3	ENST00000308580.12	c.283+3550C>T		intron_variant		1	NM_014547.5	P1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2324 AN: 152180 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00564

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0153 AC: 2336 AN: 152298 Hom.: 85 Cov.: 32 AF XY: 0.0165 AC XY: 1228 AN XY: 74468

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00564

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0205 Hom.: 58

Bravo AF: 0.0214

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.088
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10519326; hg19: chr15-52165120;