rs753545435

Variant names:

• chr1-110404034-G-A
• rs753545435
• NM_001382293.1:c.100C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-110404034-G-A
• chr1-110404034-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001382293.1(LAMTOR5):​c.100C>T​(p.Arg34Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000973 in 1,613,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: LAMTOR5 NM_001382293.1 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• 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 0 ACMG points.

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.100C>T	p.Arg34Cys	missense splice_region	Exon 3 of 4	NP_001369222.1	O43504
	LAMTOR5	NM_006402.3		c.346C>T	p.Arg116Cys	missense splice_region	Exon 3 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.100C>T	p.Arg34Cys	missense splice_region	Exon 3 of 4	ENSP00000473439.1	O43504
	LAMTOR5	ENST00000256644.8	TSL:1	c.346C>T	p.Arg116Cys	missense splice_region	Exon 3 of 4	ENSP00000256644.4	A0A8Z5A536
	LAMTOR5	ENST00000474861.6	TSL:2	c.97C>T	p.Arg33Cys	missense splice_region	Exon 3 of 4	ENSP00000434828.1	E9PLX3

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250492 AF XY: 0.0000369

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000794

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000992 AC: 145 AN: 1461376 Hom.: 0 Cov.: 30 AF XY: 0.000106 AC XY: 77 AN XY: 726986

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86154

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1111858

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74278

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000992 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
PhyloP100		5.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.60
MutPred		0.31		Gain of catalytic residue at S38 (P = 0.1038)
MVP		0.83
MPC		0.35
ClinPred		0.39	T
GERP RS		5.9
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.9
Varity_R		0.38
gMVP		0.66
Mutation Taster		=42/58	disease causing

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

Other links and lift over

dbSNP: rs753545435; hg19: chr1-110946656; COSMIC: COSV99862236; COSMIC: COSV99862236;