rs6140956

Positions:

• chr20-9521433-T-C

Variant summary

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

The NM_012261.4(LAMP5):​c.664+3205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,186 control chromosomes in the GnomAD database, including 918 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 0.098 (918 hom., cov: 32)
• Consequence: LAMP5 NM_012261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP5	NM_012261.4	c.664+3205T>C		intron_variant		ENST00000246070.3	NP_036393.1
LAMP5	NM_001199897.2	c.532+3205T>C		intron_variant			NP_001186826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP5	ENST00000246070.3	c.664+3205T>C		intron_variant		1	NM_012261.4	ENSP00000246070	P1
LAMP5	ENST00000427562.6	c.532+3205T>C		intron_variant		2		ENSP00000406360

Frequencies

GnomAD3 genomes AF: 0.0982 AC: 14930 AN: 152068 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0982 AC: 14943 AN: 152186 Hom.: 918 Cov.: 32 AF XY: 0.0999 AC XY: 7431 AN XY: 74412

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.0566

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0920

Gnomad4 OTH AF: 0.115

Alfa AF: 0.107 Hom.: 208

Bravo AF: 0.111

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.80

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: rs6140956; hg19: chr20-9502080;