rs999768591

Variant summary

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

The NM_005558.4(LAD1):​c.28G>C​(p.Ala10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

LAD1
NM_005558.4 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.958
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]

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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=0.24960572).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAD1NM_005558.4 linkc.28G>C p.Ala10Pro missense_variant Exon 1 of 10 ENST00000391967.7 NP_005549.2 O00515
LOC101929343XR_241172.3 linkn.-212C>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAD1ENST00000391967.7 linkc.28G>C p.Ala10Pro missense_variant Exon 1 of 10 1 NM_005558.4 ENSP00000375829.2 O00515
LAD1ENST00000367313.4 linkc.80+131G>C intron_variant Intron 1 of 9 1 ENSP00000356282.3 E9PDI4
LAD1ENST00000633953.1 linkc.-25G>C 5_prime_UTR_variant Exon 1 of 4 4 ENSP00000487726.1 A0A0J9YVY2
LAD1ENST00000631576.1 linkc.38+599G>C intron_variant Intron 1 of 2 4 ENSP00000488829.1 A0A0J9YYF6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.16e-7
AC:
1
AN:
1397588
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
691040
show subpopulations
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:
9.20e-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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T
Eigen
Benign
0.021
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.14
Sift
Uncertain
0.013
D
Sift4G
Uncertain
0.046
D
Polyphen
1.0
D
Vest4
0.39
MutPred
0.29
Gain of loop (P = 0.0013);
MVP
0.12
MPC
0.57
ClinPred
0.82
D
GERP RS
2.2
Varity_R
0.60
gMVP
0.075

Splicing

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: chr1-201368407; API