rs748928607

Variant names:

• chr18-23689736-C-A
• rs748928607
• NM_198129.4:c.53C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-23689736-C-A
• chr18-23689736-C-G

Variant summary

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

The NM_198129.4(LAMA3):​c.53C>A​(p.Pro18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,340,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: LAMA3 NM_198129.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

Genes affected

LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 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=0.14320049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA3	NM_198129.4	c.53C>A	p.Pro18Gln	missense_variant	Exon 1 of 75	ENST00000313654.14	NP_937762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA3	ENST00000313654.14	c.53C>A	p.Pro18Gln	missense_variant	Exon 1 of 75	1	NM_198129.4	ENSP00000324532.8
LAMA3	ENST00000399516.7	c.53C>A	p.Pro18Gln	missense_variant	Exon 1 of 74	1		ENSP00000382432.2
LAMA3	ENST00000585600.5	n.53C>A		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000468316.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000373 AC: 5 AN: 1340500 Hom.: 0 Cov.: 31 AF XY: 0.00000455 AC XY: 3 AN XY: 658764

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000162

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.90
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.045
Sift	Benign	0.26	T;T
Vest4		0.24
MutPred		0.23		Loss of glycosylation at P18 (P = 0.0202);Loss of glycosylation at P18 (P = 0.0202);
MVP		0.28
MPC		1.5
ClinPred		0.16	T
GERP RS		-0.58
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs748928607; hg19: chr18-21269700;