chr6-144423616-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_007124.3(UTRN):c.302A>T(p.His101Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
UTRN
NM_007124.3 missense
NM_007124.3 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 6.90
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UTRN | NM_007124.3 | c.302A>T | p.His101Leu | missense_variant | 5/75 | ENST00000367545.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UTRN | ENST00000367545.8 | c.302A>T | p.His101Leu | missense_variant | 5/75 | 5 | NM_007124.3 | P1 | |
UTRN | ENST00000421035.2 | c.317A>T | p.His106Leu | missense_variant | 4/6 | 2 | |||
UTRN | ENST00000628146.2 | c.275A>T | p.His92Leu | missense_variant | 4/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152254Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251456Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135900
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727240
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74388
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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 | Jun 09, 2022 | The c.302A>T (p.H101L) alteration is located in exon 4 (coding exon 4) of the UTRN gene. This alteration results from a A to T substitution at nucleotide position 302, causing the histidine (H) at amino acid position 101 to be replaced by a leucine (L). 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
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Pathogenic
D;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D
REVEL
Pathogenic
Sift
Uncertain
D;.;D
Sift4G
Benign
.;T;T
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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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