chr1-26058199-T-G

Position:

• chr1-26058199-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM63	NM_032588.4	c.831+191A>C		intron_variant		ENST00000374272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM63	ENST00000374272.4	c.831+191A>C		intron_variant		1	NM_032588.4	P1

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

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.250

Alfa AF: 0.214 Hom.: 2927

Bravo AF: 0.262

Asia WGS AF: 0.159 AC: 557 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs1317709; hg19: chr1-26384690;