6-144429721-G-A
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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
NM_007124.3 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 5.76
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]
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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 |
---|---|---|---|---|---|---|---|
UTRN | NM_007124.3 | c.835G>A | p.Glu279Lys | missense_variant | 9/75 | ENST00000367545.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UTRN | ENST00000367545.8 | c.835G>A | p.Glu279Lys | missense_variant | 9/75 | 5 | NM_007124.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247960Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134230
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458756Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 725668
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74458
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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 submitter | clinical testing | Ambry Genetics | Mar 01, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Polyphen
B
Vest4
MutPred
Gain of ubiquitination at E279 (P = 0.0185);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at