rs6133716

Positions:

• chr20-9527284-G-A
• chr20-9527284-G-T

Variant summary

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

The NM_012261.4(LAMP5):​c.665-2358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,938 control chromosomes in the GnomAD database, including 2,383 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2383 hom., cov: 31)
• Consequence: LAMP5 NM_012261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

LAMP5 (HGNC:16097): (lysosomal associated membrane protein family member 5) Predicted to be involved in establishment of protein localization to organelle. Located in endoplasmic reticulum-Golgi intermediate compartment membrane; endosome membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP5	NM_012261.4	c.665-2358G>A		intron_variant		ENST00000246070.3	NP_036393.1
LAMP5	NM_001199897.2	c.533-2358G>A		intron_variant			NP_001186826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP5	ENST00000246070.3	c.665-2358G>A		intron_variant		1	NM_012261.4	ENSP00000246070	P1
LAMP5	ENST00000427562.6	c.533-2358G>A		intron_variant		2		ENSP00000406360

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23730 AN: 151820 Hom.: 2372 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23770 AN: 151938 Hom.: 2383 Cov.: 31 AF XY: 0.156 AC XY: 11602 AN XY: 74254

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.0544

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0924

Gnomad4 OTH AF: 0.156

Alfa AF: 0.135 Hom.: 495

Bravo AF: 0.176

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.36
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs6133716; hg19: chr20-9507931;