1-46203578-C-G

Variant names:

• chr1-46203578-C-G
• NM_001013615.3:c.152C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013615.3(LURAP1):​c.152C>G​(p.Thr51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LURAP1 NM_001013615.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

Genes affected

LURAP1 (HGNC:32327): (leucine rich adaptor protein 1) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of cytokine production. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047984183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LURAP1	NM_001013615.3	c.152C>G	p.Thr51Ser	missense_variant	Exon 1 of 2	ENST00000371980.4	NP_001013633.1
POMGNT1	NM_001243766.2	c.-50-5707G>C		intron_variant	Intron 1 of 22		NP_001230695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LURAP1	ENST00000371980.4	c.152C>G	p.Thr51Ser	missense_variant	Exon 1 of 2	1	NM_001013615.3	ENSP00000361048.3
POMGNT1	ENST00000371992.1	c.-50-5707G>C		intron_variant	Intron 1 of 22	2		ENSP00000361060.1
POMGNT1	ENST00000693223.1	n.599-5707G>C		intron_variant	Intron 1 of 19

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152C>G (p.T51S) alteration is located in exon 1 (coding exon 1) of the LURAP1 gene. This alteration results from a C to G substitution at nucleotide position 152, causing the threonine (T) at amino acid position 51 to be replaced by a serine (S). 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	0.079
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.65
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.061
Sift	Benign	0.46	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.18		Loss of catalytic residue at T51 (P = 0.0036);
MVP		0.21
MPC		0.19
ClinPred		0.078	T
GERP RS		4.0
Varity_R		0.066
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-46669250;