chr6-144426347-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007124.3(UTRN):​c.466C>G​(p.Leu156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

UTRN
NM_007124.3 missense

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTRNNM_007124.3 linkuse as main transcriptc.466C>G p.Leu156Val missense_variant 7/75 ENST00000367545.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTRNENST00000367545.8 linkuse as main transcriptc.466C>G p.Leu156Val missense_variant 7/755 NM_007124.3 P1P46939-1
UTRNENST00000628146.2 linkuse as main transcriptc.439C>G p.Leu147Val missense_variant 6/62
UTRNENST00000421035.2 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsAug 31, 2022The c.466C>G (p.L156V) alteration is located in exon 6 (coding exon 6) of the UTRN gene. This alteration results from a C to G substitution at nucleotide position 466, causing the leucine (L) at amino acid position 156 to be replaced by a valine (V). 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
Uncertain
0.39
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Pathogenic
0.50
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.7
H;.
MutationTaster
Benign
0.82
D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-2.0
N;.
REVEL
Pathogenic
0.81
Sift
Benign
0.094
T;.
Sift4G
Uncertain
0.022
.;D
Polyphen
1.0
D;.
Vest4
0.94
MutPred
0.75
Gain of methylation at K154 (P = 0.0636);.;
MVP
0.84
MPC
0.59
ClinPred
0.76
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.45
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-144747483; API