rs749464893

Variant names:

• chr13-113310851-C-A
• rs749464893
• NM_005561.4:c.546C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-113310851-C-A
• chr13-113310851-C-G
• chr13-113310851-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005561.4(LAMP1):​c.546C>A​(p.Ser182Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LAMP1 NM_005561.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 1 publications found

Genes affected

LAMP1 (HGNC:6499): (lysosomal associated membrane protein 1) The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may also play a role in tumor cell metastasis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12029165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP1	NM_005561.4	c.546C>A	p.Ser182Arg	missense_variant	Exon 4 of 9	ENST00000332556.5	NP_005552.3
LAMP1	XM_011537494.3	c.489C>A	p.Ser163Arg	missense_variant	Exon 4 of 9		XP_011535796.1
LAMP1	XM_047430302.1	c.480C>A	p.Ser160Arg	missense_variant	Exon 4 of 9		XP_047286258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP1	ENST00000332556.5	c.546C>A	p.Ser182Arg	missense_variant	Exon 4 of 9	1	NM_005561.4	ENSP00000333298.4
LAMP1	ENST00000472564.1	n.2038C>A		non_coding_transcript_exon_variant	Exon 3 of 6	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461300 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726924

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000296 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.78
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.056
Sift	Benign	0.057	T
Sift4G	Benign	0.067	T
Polyphen		0.020	B
Vest4		0.22
MutPred		0.61		Gain of MoRF binding (P = 0.0305);
MVP		0.18
MPC		0.67
ClinPred		0.36	T
GERP RS		-2.0
Varity_R		0.21
gMVP		0.47
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs749464893; hg19: chr13-113965166;