chr18-6942141-A-C

Variant names:

• chr18-6942141-A-C
• rs2057501154
• NM_005559.4:c.9166T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005559.4(LAMA1):​c.9166T>G​(p.Phe3056Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. F3056L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LAMA1 NM_005559.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 0 publications found

Genes affected

LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

LAMA1 Gene-Disease associations (from GenCC):

• ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32275796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005559.4. 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
	LAMA1	NM_005559.4	MANE Select	c.9166T>G	p.Phe3056Val	missense	Exon 63 of 63	NP_005550.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA1	ENST00000389658.4	TSL:1 MANE Select	c.9166T>G	p.Phe3056Val	missense	Exon 63 of 63	ENSP00000374309.3	P25391
	LAMA1	ENST00000940203.1		c.9259T>G	p.Phe3087Val	missense	Exon 64 of 64	ENSP00000610262.1
	LAMA1	ENST00000940200.1		c.9196T>G	p.Phe3066Val	missense	Exon 63 of 63	ENSP00000610259.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.0
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.72	P
Vest4		0.38
MutPred		0.36		Loss of loop (P = 0.0986)
MVP		0.55
MPC		0.30
ClinPred		0.76	D
GERP RS		1.9
Varity_R		0.18
gMVP		0.60

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: rs2057501154; hg19: chr18-6942140;