NM_014548.4:c.284-1493A>C

Variant names:

• chr15-51772219-A-C
• rs10519323
• NM_014548.4:c.284-1493A>C

Variant summary

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

The NM_014548.4(TMOD2):​c.284-1493A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 152,276 control chromosomes in the GnomAD database, including 86 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 0.014 (86 hom., cov: 32)
• Consequence: TMOD2 NM_014548.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 0 publications found

Genes affected

TMOD2 (HGNC:11872): (tropomodulin 2) This gene encodes a neuronal-specific member of the tropomodulin family of actin-regulatory proteins. The encoded protein caps the pointed end of actin filaments preventing both elongation and depolymerization. The capping activity of this protein is dependent on its association with tropomyosin. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014548.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD2	NM_014548.4	MANE Select	c.284-1493A>C		intron	N/A	NP_055363.1
	TMOD2	NM_001142885.2		c.284-1493A>C		intron	N/A	NP_001136357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD2	ENST00000249700.9	TSL:1 MANE Select	c.284-1493A>C		intron	N/A	ENSP00000249700.4
	TMOD2	ENST00000435126.6	TSL:2	c.284-1493A>C		intron	N/A	ENSP00000404590.2
	TMOD2	ENST00000539962.6	TSL:2	c.152-1493A>C		intron	N/A	ENSP00000437743.2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2176 AN: 152156 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00565

Gnomad OTH AF: 0.0221

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

GnomAD4 genome AF: 0.0143 AC: 2181 AN: 152276 Hom.: 86 Cov.: 32 AF XY: 0.0153 AC XY: 1141 AN XY: 74472

African (AFR) AF: 0.00344 AC: 143 AN: 41568

American (AMR) AF: 0.0715 AC: 1094 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3468

East Asian (EAS) AF: 0.0720 AC: 373 AN: 5178

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4822

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00565 AC: 384 AN: 68014

Other (OTH) AF: 0.0223 AC: 47 AN: 2106

Alfa AF: 0.0199 Hom.: 65

Bravo AF: 0.0205

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		0.42
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: rs10519323; hg19: chr15-52064416;