chr15-51931220-A-G

Position:

• chr15-51931220-A-G

Variant summary

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

The ENST00000558666.1(TMOD3):​n.377A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,118 control chromosomes in the GnomAD database, including 13,609 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 0.42 (13598 hom., cov: 32)
  • Exomes 𝑓: 0.55 (11 hom.)
• Consequence: TMOD3 ENST00000558666.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

TMOD3 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC112268148	XR_002957717.2	n.351A>G		non_coding_transcript_exon_variant	2/4
LOC112268148	XR_007064635.1	n.2477-3030A>G		intron_variant
LOC112268148	XR_007064636.1	n.162-3030A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD3	ENST00000558666.1	n.377A>G		non_coding_transcript_exon_variant	2/2	3
TMOD3	ENST00000561438.5	n.*488A>G		non_coding_transcript_exon_variant	8/8	5		ENSP00000452939.1
TMOD3	ENST00000561438.5	n.*488A>G		3_prime_UTR_variant	8/8	5		ENSP00000452939.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63747 AN: 151920 Hom.: 13568 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.550 AC: 44 AN: 80 Hom.: 11 Cov.: 0 AF XY: 0.533 AC XY: 32 AN XY: 60

Gnomad4 EAS exome AF: 0.333

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.420 AC: 63829 AN: 152038 Hom.: 13598 Cov.: 32 AF XY: 0.417 AC XY: 30988 AN XY: 74310

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.462

Alfa AF: 0.441 Hom.: 2547

Bravo AF: 0.433

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2593170; hg19: chr15-52223417;