rs368202093

Variant names:

• chr9-127502879-C-G
• rs368202093
• NM_001005373.4:c.2152C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-127502879-C-G
• chr9-127502879-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001005373.4(LRSAM1):​c.2152C>G​(p.Arg718Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,458 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R718C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRSAM1 NM_001005373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 0 publications found

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: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRSAM1	NM_001005373.4	MANE Select	c.2152C>G	p.Arg718Gly	missense	Exon 26 of 26	NP_001005373.1
	LRSAM1	NM_001005374.4		c.2152C>G	p.Arg718Gly	missense	Exon 25 of 25	NP_001005374.1
	LRSAM1	NM_001384142.1		c.2152C>G	p.Arg718Gly	missense	Exon 26 of 26	NP_001371071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRSAM1	ENST00000300417.11	TSL:1 MANE Select	c.2152C>G	p.Arg718Gly	missense	Exon 26 of 26	ENSP00000300417.6
	LRSAM1	ENST00000373322.1	TSL:1	c.2152C>G	p.Arg718Gly	missense	Exon 25 of 25	ENSP00000362419.1
	LRSAM1	ENST00000676170.1		c.2233C>G	p.Arg745Gly	missense	Exon 27 of 27	ENSP00000502177.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453458 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 722576

African (AFR) AF: 0.00 AC: 0 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 85006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5300

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108950

Other (OTH) AF: 0.00 AC: 0 AN: 60020

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		3.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.028	D
Polyphen		0.75	P
Vest4		0.63
MutPred		0.48		Loss of helix (P = 0.0033)
MVP		0.65
MPC		0.60
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.60
gMVP		0.88
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs368202093; hg19: chr9-130265158;