rs574202204

Variant names:

• chr9-127497299-T-A
• NM_001005373.4:c.1877T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-127497299-T-A
• chr9-127497299-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001005373.4(LRSAM1):​c.1877T>A​(p.Val626Asp) 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 1,460,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRSAM1 NM_001005373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRSAM1	NM_001005373.4	c.1877T>A	p.Val626Asp	missense_variant	Exon 24 of 26	ENST00000300417.11	NP_001005373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRSAM1	ENST00000300417.11	c.1877T>A	p.Val626Asp	missense_variant	Exon 24 of 26	1	NM_001005373.4	ENSP00000300417.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460664 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T;.;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T;D;.;.
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.69	N;.;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.19	B;B;B;B
Vest4		0.75
MutPred		0.71		Gain of disorder (P = 0.022);.;Gain of disorder (P = 0.022);Gain of disorder (P = 0.022);
MVP		0.66
MPC		0.37
ClinPred		0.96	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-130259578;