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6-144428886-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_007124.3(UTRN):c.687T>C(p.Asp229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000838 in 1,601,680 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00044 ( 5 hom. )

Consequence

UTRN
NM_007124.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.30
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 Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-144428886-T-C is Benign according to our data. Variant chr6-144428886-T-C is described in ClinVar as [Benign]. Clinvar id is 733657.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.3 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (710/152338) while in subpopulation AFR AF= 0.0161 (671/41580). AF 95% confidence interval is 0.0151. There are 4 homozygotes in gnomad4. There are 356 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTRNNM_007124.3 linkuse as main transcriptc.687T>C p.Asp229= synonymous_variant 8/75 ENST00000367545.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTRNENST00000367545.8 linkuse as main transcriptc.687T>C p.Asp229= synonymous_variant 8/755 NM_007124.3 P1P46939-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00467
AC:
711
AN:
152220
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0162
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00124
AC:
303
AN:
243380
Hom.:
3
AF XY:
0.000858
AC XY:
113
AN XY:
131650
show subpopulations
Gnomad AFR exome
AF:
0.0171
Gnomad AMR exome
AF:
0.000558
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000702
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000269
Gnomad OTH exome
AF:
0.000841
GnomAD4 exome
AF:
0.000437
AC:
633
AN:
1449342
Hom.:
5
Cov.:
27
AF XY:
0.000359
AC XY:
259
AN XY:
721358
show subpopulations
Gnomad4 AFR exome
AF:
0.0162
Gnomad4 AMR exome
AF:
0.000561
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000237
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000905
Gnomad4 OTH exome
AF:
0.00104
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00466
AC:
710
AN:
152338
Hom.:
4
Cov.:
32
AF XY:
0.00478
AC XY:
356
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0161
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00614
Alfa
AF:
0.00250
Hom.:
0
Bravo
AF:
0.00522
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 01, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
8.6
Dann
Benign
0.64

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

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

Other links and lift over

dbSNP: rs114053210; hg19: chr6-144750022; API