Variant 1-201389199-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005558.4(LAD1):c.143T>G(p.Leu48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LAD1
NM_005558.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0960

Variant links:

Genes affected

LAD1 (HGNC:6472): (ladinin 1) The protein encoded by this gene may be an anchoring filament that is a component of basement membranes. It may contribute to the stability of the association of the epithelial layers with the underlying mesenchyme. [provided by RefSeq, Jul 2008]

LAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10297692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAD1	NM_005558.4 linkuse as main transcript	c.143T>G	p.Leu48Arg	missense_variant	2/10	ENST00000391967.7	NP_005549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAD1	ENST00000391967.7 linkuse as main transcript	c.143T>G	p.Leu48Arg	missense_variant	2/10	1	NM_005558.4	ENSP00000375829	P3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251256

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

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

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.143T>G (p.L48R) alteration is located in exon 2 (coding exon 2) of the LAD1 gene. This alteration results from a T to G substitution at nucleotide position 143, causing the leucine (L) at amino acid position 48 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.;.;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.68

T;T;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

N;N;.;.;.

REVEL

Benign

0.073

Sift

Uncertain

0.011

D;D;.;.;.

Sift4G

Benign

0.12

T;T;.;.;T

Polyphen

0.81

P;D;.;.;.

Vest4

0.26

MutPred

0.34

.;Gain of MoRF binding (P = 0.0473);.;.;.;

MVP

0.14

MPC

0.54

ClinPred

0.19

GERP RS

0.95

Varity_R

0.12

gMVP

0.021

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over