6-144292201-C-T

Position:

• chr6-144292201-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007124.3(UTRN):​c.79+294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,992 control chromosomes in the GnomAD database, including 21,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (21620 hom., cov: 32)
• Consequence: UTRN NM_007124.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460

Genes affected

UTRN (HGNC:12635): (utrophin) This gene shares both structural and functional similarities with the dystrophin gene. It contains an actin-binding N-terminus, a triple coiled-coil repeat central region, and a C-terminus that consists of protein-protein interaction motifs which interact with dystroglycan protein components. The protein encoded by this gene is located at the neuromuscular synapse and myotendinous junctions, where it participates in post-synaptic membrane maintenance and acetylcholine receptor clustering. Mouse studies suggest that this gene may serve as a functional substitute for the dystrophin gene and therefore, may serve as a potential therapeutic alternative to muscular dystrophy which is caused by mutations in the dystrophin gene. Alternative splicing of the utrophin gene has been described; however, the full-length nature of these variants has not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-144292201-C-T is Benign according to our data. Variant chr6-144292201-C-T is described in ClinVar as [Benign]. Clinvar id is 1248204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTRN	NM_007124.3	c.79+294C>T		intron_variant		ENST00000367545.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTRN	ENST00000367545.8	c.79+294C>T		intron_variant		5	NM_007124.3	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78049 AN: 151872 Hom.: 21588 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.514 AC: 78133 AN: 151992 Hom.: 21620 Cov.: 32 AF XY: 0.510 AC XY: 37847 AN XY: 74278

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.507

Alfa AF: 0.408 Hom.: 5444

Bravo AF: 0.529

Asia WGS AF: 0.521 AC: 1812 AN: 3476

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.59

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: rs592667; hg19: chr6-144613337;