1-209618555-G-T

Position:

• chr1-209618555-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000356082.9(LAMB3):​c.2806C>A​(p.Gln936Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: LAMB3 ENST00000356082.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37950662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB3	NM_000228.3	c.2806C>A	p.Gln936Lys	missense_variant	19/23	ENST00000356082.9	NP_000219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB3	ENST00000356082.9	c.2806C>A	p.Gln936Lys	missense_variant	19/23	1	NM_000228.3	ENSP00000348384	P1
LAMB3	ENST00000367030.7	c.2806C>A	p.Gln936Lys	missense_variant	19/23	1		ENSP00000355997	P1
LAMB3	ENST00000391911.5	c.2806C>A	p.Gln936Lys	missense_variant	18/22	1		ENSP00000375778	P1
LAMB3	ENST00000455193.1	c.13C>A	p.Gln5Lys	missense_variant	1/4	2		ENSP00000398683

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152242 Hom.: 0 Cov.: 34 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152360 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74512

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T;T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.80	.;T;.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.0	M;M;M;.
MutationTaster	Benign	0.86	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.34	N;N;N;N
REVEL	Benign	0.099
Sift	Benign	0.20	T;T;T;T
Sift4G	Uncertain	0.055	T;T;T;.
Polyphen		0.95	P;P;P;.
Vest4		0.20
MutPred		0.30		Gain of ubiquitination at Q936 (P = 0.0162);Gain of ubiquitination at Q936 (P = 0.0162);Gain of ubiquitination at Q936 (P = 0.0162);.;
MVP		0.86
MPC		0.33
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.35

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: chr1-209791900;