15-51931220-A-G

Variant names:

• chr15-51931220-A-G
• rs2593170
• ENST00000558666.1:n.377A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

LOC112268148 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558666.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD3	ENST00000558666.1	TSL:3	n.377A>G		non_coding_transcript_exon	Exon 2 of 2
	TMOD3	ENST00000561438.5	TSL:5	n.*488A>G		non_coding_transcript_exon	Exon 8 of 8	ENSP00000452939.1	H0YKU1
	TMOD3	ENST00000561438.5	TSL:5	n.*488A>G		3_prime_UTR	Exon 8 of 8	ENSP00000452939.1	H0YKU1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.556 AC: 40 AN: 72

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.413 AC: 17134 AN: 41446

American (AMR) AF: 0.513 AC: 7840 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3472

East Asian (EAS) AF: 0.355 AC: 1840 AN: 5178

South Asian (SAS) AF: 0.327 AC: 1580 AN: 4826

European-Finnish (FIN) AF: 0.404 AC: 4262 AN: 10550

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28119 AN: 67960

Other (OTH) AF: 0.462 AC: 976 AN: 2112

Alfa AF: 0.440 Hom.: 2605

Bravo AF: 0.433

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-0.049

Splicing

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

Other links and lift over

dbSNP: rs2593170; hg19: chr15-52223417;