1-26058199-T-G

Variant names:

• chr1-26058199-T-G
• rs1317709
• NM_032588.4:c.831+191A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032588.4(TRIM63):​c.831+191A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,026 control chromosomes in the GnomAD database, including 5,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5301 hom., cov: 32)
• Consequence: TRIM63 NM_032588.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-26058199-T-G is Benign according to our data. Variant chr1-26058199-T-G is described in ClinVar as Benign. ClinVar VariationId is 1226300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 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.831+191A>C		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.831+191A>C		intron	N/A	ENSP00000363390.3	Q969Q1-1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37888 AN: 151906 Hom.: 5292 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.250 AC: 37942 AN: 152026 Hom.: 5301 Cov.: 32 AF XY: 0.245 AC XY: 18176 AN XY: 74326

African (AFR) AF: 0.380 AC: 15730 AN: 41432

American (AMR) AF: 0.208 AC: 3181 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.190 AC: 984 AN: 5170

South Asian (SAS) AF: 0.104 AC: 500 AN: 4812

European-Finnish (FIN) AF: 0.187 AC: 1980 AN: 10572

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14162 AN: 67976

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.219 Hom.: 4165

Bravo AF: 0.262

Asia WGS AF: 0.159 AC: 557 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
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.53
PhyloP100		0.67
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: rs1317709; hg19: chr1-26384690;