6-144429721-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007124.3(UTRN):​c.835G>A​(p.Glu279Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,611,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

UTRN
NM_007124.3 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.103022724).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTRNNM_007124.3 linkuse as main transcriptc.835G>A p.Glu279Lys missense_variant 9/75 ENST00000367545.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTRNENST00000367545.8 linkuse as main transcriptc.835G>A p.Glu279Lys missense_variant 9/755 NM_007124.3 P1P46939-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000579
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
247960
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134230
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000331
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1458756
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
2
AN XY:
725668
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000152
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152260
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 01, 2024The c.835G>A (p.E279K) alteration is located in exon 8 (coding exon 8) of the UTRN gene. This alteration results from a G to A substitution at nucleotide position 835, causing the glutamic acid (E) at amino acid position 279 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T
Eigen
Benign
-0.078
Eigen_PC
Benign
0.095
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.76
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.15
Sift
Benign
0.16
T
Polyphen
0.058
B
Vest4
0.43
MutPred
0.45
Gain of ubiquitination at E279 (P = 0.0185);
MVP
0.48
MPC
0.24
ClinPred
0.17
T
GERP RS
5.5
Varity_R
0.14
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs565968197; hg19: chr6-144750857; API