chr1-26054237-C-CT

Variant names:

• chr1-26054237-C-CT
• rs11424290
• NM_032588.4:c.980-274_980-273insA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032588.4(TRIM63):​c.980-274_980-273insA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49768 hom., cov: 0)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113
• Publications: 0 publications found

Genes affected

TRIM63 (HGNC:16007): (tripartite motif containing 63) This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is an E3 ubiquitin ligase that localizes to the Z-line and M-line lattices of myofibrils. This protein plays an important role in the atrophy of skeletal and cardiac muscle and is required for the degradation of myosin heavy chain proteins, myosin light chain, myosin binding protein, and for muscle-type creatine kinase. [provided by RefSeq, Feb 2012]

TRIM63 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AR, AD Classification: MODERATE, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-26054237-C-CT is Benign according to our data. Variant chr1-26054237-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1269179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032588.4. 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
	TRIM63	NM_032588.4	MANE Select	c.980-274_980-273insA		intron	N/A	NP_115977.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM63	ENST00000374272.4	TSL:1 MANE Select	c.980-274_980-273insA		intron	N/A	ENSP00000363390.3	Q969Q1-1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120980 AN: 152034 Hom.: 49741 Cov.: 0

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.789

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.796 AC: 121050 AN: 152152 Hom.: 49768 Cov.: 0 AF XY: 0.799 AC XY: 59446 AN XY: 74402

African (AFR) AF: 0.578 AC: 23982 AN: 41476

American (AMR) AF: 0.869 AC: 13279 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2602 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4179 AN: 5180

South Asian (SAS) AF: 0.819 AC: 3951 AN: 4822

European-Finnish (FIN) AF: 0.958 AC: 10162 AN: 10608

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60164 AN: 67990

Other (OTH) AF: 0.792 AC: 1673 AN: 2112

Alfa AF: 0.833 Hom.: 6537

Bravo AF: 0.782

Asia WGS AF: 0.841 AC: 2924 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11424290; hg19: chr1-26380728;