NM_005559.4:c.9220G>C

Variant names:

• chr18-6942087-C-G
• NM_005559.4:c.9220G>C

Variant summary

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

The NM_005559.4(LAMA1):​c.9220G>C​(p.Glu3074Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAMA1 NM_005559.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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]

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=0.14903617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.9220G>C	p.Glu3074Gln	missense_variant	Exon 63 of 63	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.9220G>C	p.Glu3074Gln	missense_variant	Exon 63 of 63	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000488064.5	n.2627G>C		non_coding_transcript_exon_variant	Exon 14 of 14	2
LAMA1	ENST00000492048.5	n.2108G>C		non_coding_transcript_exon_variant	Exon 7 of 7	2
LAMA1	ENST00000579014.5	n.10235G>C		non_coding_transcript_exon_variant	Exon 62 of 62	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.044
Sift	Benign	0.099	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.24	B
Vest4		0.11
MutPred		0.25		Loss of glycosylation at S3069 (P = 0.0936);
MVP		0.39
MPC		0.12
ClinPred		0.23	T
GERP RS		4.9
Varity_R		0.11
gMVP		0.44

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: chr18-6942086;