rs10519324

chr15-51773628-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014548.4(TMOD2):c.284-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,403,874 control chromosomes in the GnomAD database, including 41 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 0.0092 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (26 hom.)
• Consequence: TMOD2 NM_014548.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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=-0.72).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00921 (1403/152288) while in subpopulation AFR AF= 0.0185 (767/41562). AF 95% confidence interval is 0.0174. There are 15 homozygotes in gnomad4. There are 636 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMOD2	NM_014548.4	c.284-84C>T		intron_variant		ENST00000249700.9
TMOD2	NM_001142885.2	c.284-84C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMOD2	ENST00000249700.9	c.284-84C>T		intron_variant		1	NM_014548.4	P1
TMOD2	ENST00000435126.6	c.284-84C>T		intron_variant		2
TMOD2	ENST00000539962.6	c.152-84C>T		intron_variant		2
TMOD2	ENST00000560576.1	n.796+6558C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00921 AC: 1402 AN: 152170 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00820

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.00719

GnomAD4 exome AF: 0.00609 AC: 7620 AN: 1251586 Hom.: 26 AF XY: 0.00606 AC XY: 3763 AN XY: 620964

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.00321

Gnomad4 ASJ exome AF: 0.000434

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.00438

Gnomad4 FIN exome AF: 0.00752

Gnomad4 NFE exome AF: 0.00621

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.00921 AC: 1403 AN: 152288 Hom.: 15 Cov.: 32 AF XY: 0.00854 AC XY: 636 AN XY: 74458

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.00820

Gnomad4 NFE AF: 0.00650

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00906 Hom.: 6

Bravo AF: 0.00901

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	9.5
Dann	Benign	0.74

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: rs10519324; hg19: chr15-52065825;