rs999768591

Variant names:

• chr1-201399279-C-G
• NM_005558.4:c.28G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-201399279-C-G
• chr1-201399279-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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 𝑓: 7.2e-7 (0 hom.)
• Consequence: LAD1 NM_005558.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958

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]

LOC101929343 (HGNC:):

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=0.24960572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAD1	NM_005558.4	c.28G>C	p.Ala10Pro	missense_variant	Exon 1 of 10	ENST00000391967.7	NP_005549.2
LOC101929343	XR_241172.3	n.-212C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAD1	ENST00000391967.7	c.28G>C	p.Ala10Pro	missense_variant	Exon 1 of 10	1	NM_005558.4	ENSP00000375829.2
LAD1	ENST00000367313.4	c.80+131G>C		intron_variant	Intron 1 of 9	1		ENSP00000356282.3
LAD1	ENST00000633953.1	c.-25G>C		5_prime_UTR_variant	Exon 1 of 4	4		ENSP00000487726.1
LAD1	ENST00000631576.1	c.38+599G>C		intron_variant	Intron 1 of 2	4		ENSP00000488829.1

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

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;