NM_001382293.1:c.238G>C

Variant names:

• chr1-110401561-C-G
• rs780723150
• NM_001382293.1:c.238G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001382293.1(LAMTOR5):​c.238G>C​(p.Asp80His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,454,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D80N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LAMTOR5 NM_001382293.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37804466).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382293.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMTOR5	NM_001382293.1	MANE Select	c.238G>C	p.Asp80His	missense	Exon 4 of 4	NP_001369222.1	O43504
	LAMTOR5	NM_006402.3		c.484G>C	p.Asp162His	missense	Exon 4 of 4	NP_006393.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMTOR5	ENST00000602318.6	TSL:1 MANE Select	c.238G>C	p.Asp80His	missense	Exon 4 of 4	ENSP00000473439.1	O43504
	LAMTOR5	ENST00000256644.8	TSL:1	c.484G>C	p.Asp162His	missense	Exon 4 of 4	ENSP00000256644.4	A0A8Z5A536
	LAMTOR5	ENST00000474861.6	TSL:2	c.235G>C	p.Asp79His	missense	Exon 4 of 4	ENSP00000434828.1	E9PLX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454662 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722032

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.00 AC: 0 AN: 85786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106100

Other (OTH) AF: 0.0000166 AC: 1 AN: 60126

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.30	T
PhyloP100		5.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.023	D
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.47
MutPred		0.40		Loss of ubiquitination at K78 (P = 0.0768)
MVP		0.75
MPC		0.94
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.93
gMVP		0.78
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs780723150; hg19: chr1-110944183;