rs773899723

Positions:

• chr9-127501138-C-G
• chr9-127501138-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001005373.4(LRSAM1):​c.2041C>G​(p.Arg681Gly) 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 benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRSAM1 NM_001005373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a zinc_finger_region RING-type (size 35) in uniprot entity LRSM1_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_001005373.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31205845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRSAM1	NM_001005373.4	c.2041C>G	p.Arg681Gly	missense_variant	25/26	ENST00000300417.11	NP_001005373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRSAM1	ENST00000300417.11	c.2041C>G	p.Arg681Gly	missense_variant	25/26	1	NM_001005373.4	ENSP00000300417	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	0.0043	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T;.;T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.66	T;T;.;.
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.2	L;.;L;L
MutationTaster	Benign	0.91	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.093	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.25	B;B;B;B
Vest4		0.62
MutPred		0.27		Gain of sheet (P = 0.0166);.;Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);
MVP		0.79
MPC		0.31
ClinPred		0.66	D
GERP RS		4.2
Varity_R		0.23
gMVP		0.66

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: chr9-130263417;