1-110401579-T-C

Variant names:

• chr1-110401579-T-C
• rs1187012460
• NM_001382293.1:c.220A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382293.1(LAMTOR5):​c.220A>G​(p.Ile74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LAMTOR5 NM_001382293.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

Genes affected

LAMTOR5 (HGNC:17955): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 5) This gene encodes a protein that specifically complexes with the C-terminus of hepatitis B virus X protein (HBx). The function of this protein is to negatively regulate HBx activity and thus to alter the replication life cycle of the virus. [provided by RefSeq, Jul 2008]

LAMTOR5-AS1 (HGNC:40823): (LAMTOR5 and SLC16A4 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112348765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMTOR5	NM_001382293.1	c.220A>G	p.Ile74Val	missense_variant	Exon 4 of 4	ENST00000602318.6	NP_001369222.1
LAMTOR5	NM_006402.3	c.466A>G	p.Ile156Val	missense_variant	Exon 4 of 4		NP_006393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMTOR5	ENST00000602318.6	c.220A>G	p.Ile74Val	missense_variant	Exon 4 of 4	1	NM_001382293.1	ENSP00000473439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250884 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135708

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1451428 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 719592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.466A>G (p.I156V) alteration is located in exon 4 (coding exon 4) of the LAMTOR5 gene. This alteration results from a A to G substitution at nucleotide position 466, causing the isoleucine (I) at amino acid position 156 to be replaced by a valine (V). 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	Benign	0.083
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T;T;T;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.66	.;T;T;.;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.17	N;N;.;N;.;.
REVEL	Benign	0.039
Sift	Benign	0.42	T;T;.;T;.;.
Sift4G	Benign	0.41	T;T;T;T;T;T
Polyphen		0.0060	.;.;B;.;.;.
Vest4		0.13
MutPred		0.38		.;.;Loss of ubiquitination at K78 (P = 0.1306);.;.;.;
MVP		0.70
MPC		0.22
ClinPred		0.91	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.28
gMVP		0.51

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: rs1187012460; hg19: chr1-110944201;