LMAN1 p.Val487Val

Variant names:

• chr18-59331452-G-G
• NM_005570.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr18-59331453--
• chr18-59331453-C-A
• chr18-59331453-C-G
• chr18-59331453-C-T

Variant summary

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

The NM_005570.4(LMAN1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMAN1 NM_005570.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• Publications: 0 publications found

Genes affected

LMAN1 (HGNC:6631): (lectin, mannose binding 1) The protein encoded by this gene is a membrane mannose-specific lectin that cycles between the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment, and cis-Golgi, functioning as a cargo receptor for glycoprotein transport. The protein has an N-terminal signal sequence, a calcium-dependent and pH-sensitive carbohydrate recognition domain, a stalk region that functions in oligomerization, a transmembrane domain, and a short cytoplasmic domain required for organelle targeting. Allelic variants of this gene are associated with the autosomal recessive disorder combined factor V-factor VIII deficiency. [provided by RefSeq, Jul 2015]

LMAN1 Gene-Disease associations (from GenCC):

• factor V and factor VIII, combined deficiency of, type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
• combined deficiency of factor V and factor VIII

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000267677 (HGNC:):

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_005570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMAN1	NM_005570.4	MANE Select	c.		exon_region	Exon 12 of 13	NP_005561.1	P49257

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMAN1	ENST00000251047.6	TSL:1 MANE Select	c.		exon_region	Exon 12 of 13	ENSP00000251047.4	P49257
	LMAN1	ENST00000963587.1		c.		exon_region	Exon 12 of 13	ENSP00000633646.1
	LMAN1	ENST00000904707.1		c.		exon_region	Exon 12 of 13	ENSP00000574766.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-56998684;