rs79882576

Variant names:

• chr9-35683152-G-A
• rs79882576
• NM_003289.4:c.*7C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-35683152-G-A
• chr9-35683152-G-C
• chr9-35683152-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003289.4(TPM2):​c.*7C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,553,072 control chromosomes in the GnomAD database, including 565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (305 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (260 hom.)
• Consequence: TPM2 NM_003289.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.712
• Publications: 4 publications found

Genes affected

TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

TPM2 Gene-Disease associations (from GenCC):

• TPM2-related myopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• arthrogryposis, distal, type 1A

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• congenital myopathy 23

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• congenital myopathy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• cap myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• childhood-onset nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Sheldon-hall syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• typical nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 9-35683152-G-A is Benign according to our data. Variant chr9-35683152-G-A is described in ClinVar as Benign. ClinVar VariationId is 94121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003289.4. 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
	TPM2	NM_003289.4	MANE Select	c.*7C>T		3_prime_UTR	Exon 9 of 9	NP_003280.2
	TPM2	NM_001301227.2		c.*7C>T		3_prime_UTR	Exon 9 of 9	NP_001288156.1
	TPM2	NM_001301226.2		c.773-989C>T		intron	N/A	NP_001288155.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPM2	ENST00000645482.3	MANE Select	c.*7C>T		3_prime_UTR	Exon 9 of 9	ENSP00000496494.2
	TPM2	ENST00000378292.9	TSL:1	c.773-989C>T		intron	N/A	ENSP00000367542.3
	TPM2	ENST00000951580.1		c.*7C>T		3_prime_UTR	Exon 10 of 10	ENSP00000621639.1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5421 AN: 152150 Hom.: 303 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.00829 AC: 1320 AN: 159324 AF XY: 0.00604

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00614

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000868

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000226

Gnomad OTH exome AF: 0.00464

GnomAD4 exome AF: 0.00360 AC: 5038 AN: 1400806 Hom.: 260 Cov.: 33 AF XY: 0.00307 AC XY: 2120 AN XY: 691070

African (AFR) AF: 0.124 AC: 3930 AN: 31642

American (AMR) AF: 0.00698 AC: 251 AN: 35958

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25266

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35836

South Asian (SAS) AF: 0.000390 AC: 31 AN: 79448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49370

Middle Eastern (MID) AF: 0.00825 AC: 47 AN: 5700

European-Non Finnish (NFE) AF: 0.000204 AC: 220 AN: 1079508

Other (OTH) AF: 0.00959 AC: 557 AN: 58078

GnomAD4 genome AF: 0.0358 AC: 5444 AN: 152266 Hom.: 305 Cov.: 33 AF XY: 0.0338 AC XY: 2517 AN XY: 74450

African (AFR) AF: 0.124 AC: 5134 AN: 41516

American (AMR) AF: 0.0154 AC: 235 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68026

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0126 Hom.: 59

Bravo AF: 0.0407

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Arthrogryposis, distal, type 1A (1)
-	-	1	Congenital myopathy 23 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.5
DANN	Benign	0.84
PhyloP100		0.71
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: rs79882576; hg19: chr9-35683149;