rs10519323

Positions:

• chr15-51772219-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMOD2	NM_014548.4	c.284-1493A>C		intron_variant		ENST00000249700.9	NP_055363.1
TMOD2	NM_001142885.2	c.284-1493A>C		intron_variant			NP_001136357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD2	ENST00000249700.9	c.284-1493A>C		intron_variant		1	NM_014548.4	ENSP00000249700	P1
TMOD2	ENST00000435126.6	c.284-1493A>C		intron_variant		2		ENSP00000404590
TMOD2	ENST00000539962.6	c.152-1493A>C		intron_variant		2		ENSP00000437743
TMOD2	ENST00000560576.1	n.796+5149A>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.0720

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00565

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0205 Hom.: 58

Bravo AF: 0.0205

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.65

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: rs10519323; hg19: chr15-52064416;