chr20-9529781-G-T

Position:

• chr20-9529781-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012261.4(LAMP5):​c.804G>T​(p.Gln268His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAMP5 NM_012261.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMP5	NM_012261.4	c.804G>T	p.Gln268His	missense_variant	6/6	ENST00000246070.3
LAMP5	NM_001199897.2	c.672G>T	p.Gln224His	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMP5	ENST00000246070.3	c.804G>T	p.Gln268His	missense_variant	6/6	1	NM_012261.4	P1
LAMP5	ENST00000427562.6	c.672G>T	p.Gln224His	missense_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.804G>T (p.Q268H) alteration is located in exon 6 (coding exon 6) of the LAMP5 gene. This alteration results from a G to T substitution at nucleotide position 804, causing the glutamine (Q) at amino acid position 268 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.77
MutPred		0.23		.;Loss of MoRF binding (P = 0.0975);
MVP		0.34
MPC		0.36
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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: chr20-9510428; COSMIC: COSV55715139;