rs9577229

Positions:

• chr13-113319517-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005561.4(LAMP1):​c.611C>T​(p.Ala204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,613,710 control chromosomes in the GnomAD database, including 1,626 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.054 (613 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1013 hom.)
• Consequence: LAMP1 NM_005561.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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]

LAMP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015163422).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP1	NM_005561.4	c.611C>T	p.Ala204Val	missense_variant	5/9	ENST00000332556.5	NP_005552.3
LAMP1	XM_011537494.3	c.554C>T	p.Ala185Val	missense_variant	5/9		XP_011535796.1
LAMP1	XM_047430302.1	c.545C>T	p.Ala182Val	missense_variant	5/9		XP_047286258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP1	ENST00000332556.5	c.611C>T	p.Ala204Val	missense_variant	5/9	1	NM_005561.4	ENSP00000333298.4
LAMP1	ENST00000472564.1	n.2103C>T		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8222 AN: 152170 Hom.: 612 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0314 AC: 7766 AN: 247380 Hom.: 468 AF XY: 0.0261 AC XY: 3508 AN XY: 134314

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.0610

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.00311

Gnomad FIN exome AF: 0.00776

Gnomad NFE exome AF: 0.000699

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.0110 AC: 16086 AN: 1461422 Hom.: 1013 Cov.: 31 AF XY: 0.0100 AC XY: 7297 AN XY: 727022

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0583

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.00328

Gnomad4 FIN exome AF: 0.00613

Gnomad4 NFE exome AF: 0.000512

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0542 AC: 8251 AN: 152288 Hom.: 613 Cov.: 33 AF XY: 0.0541 AC XY: 4029 AN XY: 74462

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.00641

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0146 Hom.: 199

Bravo AF: 0.0634

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.154 AC: 623

ESP6500EA AF: 0.000835 AC: 7

ExAC AF: 0.0308 AC: 3730

Asia WGS AF: 0.0530 AC: 186 AN: 3478

EpiCase AF: 0.000873

EpiControl AF: 0.000771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.86
DANN	Benign	0.95
DEOGEN2	Benign	0.082	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.59	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.014
Sift	Benign	0.30	T
Sift4G	Benign	0.30	T
Polyphen		0.017	B
Vest4		0.038
MPC		0.27
ClinPred		0.0056	T
GERP RS		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9577229; hg19: chr13-113973832; COSMIC: COSV60210590; COSMIC: COSV60210590;