NM_014547.5:c.-74-8682T>C

Variant names:

• chr15-51854129-T-C
• rs10519325
• NM_014547.5:c.-74-8682T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014547.5(TMOD3):​c.-74-8682T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,264 control chromosomes in the GnomAD database, including 84 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 (84 hom., cov: 32)
• Consequence: TMOD3 NM_014547.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 0 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014547.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD3	NM_014547.5	MANE Select	c.-74-8682T>C		intron	N/A	NP_055362.1	Q9NYL9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD3	ENST00000308580.12	TSL:1 MANE Select	c.-74-8682T>C		intron	N/A	ENSP00000308753.7	Q9NYL9
	TMOD3	ENST00000871171.1		c.-143-7725T>C		intron	N/A	ENSP00000541230.1
	TMOD3	ENST00000871172.1		c.-74-8682T>C		intron	N/A	ENSP00000541231.1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2273 AN: 152146 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0739

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: 0.00563

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0149 AC: 2276 AN: 152264 Hom.: 84 Cov.: 32 AF XY: 0.0160 AC XY: 1188 AN XY: 74440

African (AFR) AF: 0.00481 AC: 200 AN: 41554

American (AMR) AF: 0.0741 AC: 1132 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.0725 AC: 376 AN: 5184

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4822

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00563 AC: 383 AN: 68028

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0201 Hom.: 69

Bravo AF: 0.0211

Asia WGS AF: 0.0520 AC: 180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.58
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: rs10519325; hg19: chr15-52146326;