9-127461226-C-G

Variant names:

• chr9-127461226-C-G
• NM_001005373.4:c.375C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005373.4(LRSAM1):​c.375C>G​(p.Asn125Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRSAM1 NM_001005373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22539958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRSAM1	NM_001005373.4	c.375C>G	p.Asn125Lys	missense_variant	Exon 8 of 26	ENST00000300417.11	NP_001005373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRSAM1	ENST00000300417.11	c.375C>G	p.Asn125Lys	missense_variant	Exon 8 of 26	1	NM_001005373.4	ENSP00000300417.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460016 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726286

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;.;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T;T;.;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.96	L;L;L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.59	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.38	T;T;T;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.22	B;B;B;B
Vest4		0.28
MutPred		0.42		Gain of methylation at N125 (P = 0.0226);Gain of methylation at N125 (P = 0.0226);Gain of methylation at N125 (P = 0.0226);Gain of methylation at N125 (P = 0.0226);
MVP		0.41
MPC		0.20
ClinPred		0.36	T
GERP RS		6.2
Varity_R		0.056
gMVP		0.17

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: chr9-130223505;