rs869320671

Variant names:

• chr1-209615359-G-A
• NM_000228.3:c.3431C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-209615359-G-A
• chr1-209615359-G-T

Variant summary

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

The NM_000228.3(LAMB3):​c.3431C>T​(p.Ser1144Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,750 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1144S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAMB3 NM_000228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82

Genes affected

LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB3	NM_000228.3	c.3431C>T	p.Ser1144Leu	missense_variant	Exon 23 of 23	ENST00000356082.9	NP_000219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB3	ENST00000356082.9	c.3431C>T	p.Ser1144Leu	missense_variant	Exon 23 of 23	1	NM_000228.3	ENSP00000348384.3
LAMB3	ENST00000367030.7	c.3431C>T	p.Ser1144Leu	missense_variant	Exon 23 of 23	1		ENSP00000355997.3
LAMB3	ENST00000391911.5	c.3431C>T	p.Ser1144Leu	missense_variant	Exon 22 of 22	1		ENSP00000375778.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460750 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726664

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: 9.00e-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	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	.;D;.
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.069	T;T;T
Polyphen		0.66	P;P;P
Vest4		0.58
MutPred		0.38		Loss of phosphorylation at S1144 (P = 0.0597);Loss of phosphorylation at S1144 (P = 0.0597);Loss of phosphorylation at S1144 (P = 0.0597);
MVP		0.68
MPC		0.23
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.20
gMVP		0.62

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: chr1-209788704;