GeneBe

rs886063451

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138361.5(LRSAM1):​c.-338G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LRSAM1
NM_138361.5 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.89

Publications

0 publications found
Variant links:
Genes affected
LRSAM1 (HGNC:25135): (leucine rich repeat and sterile alpha motif containing 1) This gene encodes a ring finger protein involved in a variety of functions, including regulation of signaling pathways and cell adhesion, mediation of self-ubiquitylation, and involvement in cargo sorting during receptor endocytosis. Mutations in this gene have been associated with Charcot-Marie-Tooth disease. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jan 2012]
LRSAM1 Gene-Disease associations (from GenCC):
  • Charcot-Marie-Tooth disease axonal type 2P
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138361.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LRSAM1
NM_001005373.4
MANE Select
c.-189+110G>A
intron
N/ANP_001005373.1Q6UWE0-1
LRSAM1
NM_138361.5
c.-338G>A
5_prime_UTR
Exon 1 of 25NP_612370.3Q6UWE0-1
LRSAM1
NM_001384142.1
c.-1206+110G>A
intron
N/ANP_001371071.1Q6UWE0-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LRSAM1
ENST00000300417.11
TSL:1 MANE Select
c.-189+110G>A
intron
N/AENSP00000300417.6Q6UWE0-1
LRSAM1
ENST00000870580.1
c.-338G>A
5_prime_UTR
Exon 1 of 25ENSP00000540639.1
LRSAM1
ENST00000942486.1
c.-338G>A
5_prime_UTR
Exon 1 of 25ENSP00000612545.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
24988
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
13342
African (AFR)
AF:
0.00
AC:
0
AN:
1042
American (AMR)
AF:
0.00
AC:
0
AN:
1770
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
824
East Asian (EAS)
AF:
0.00
AC:
0
AN:
1398
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2552
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
858
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
106
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
15044
Other (OTH)
AF:
0.00
AC:
0
AN:
1394
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Charcot-Marie-Tooth disease axonal type 2P (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.64
DANN
Benign
0.87
PhyloP100
-1.9
PromoterAI
0.0012
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs886063451; hg19: chr9-130214058; API