9-12775888-G-C

Variant names:

• chr9-12775888-G-C
• rs1688795485
• NM_203403.2:c.173G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203403.2(LURAP1L):​c.173G>C​(p.Ser58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S58G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LURAP1L NM_203403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

Genes affected

LURAP1L (HGNC:31452): (leucine rich adaptor protein 1 like) Predicted to be involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. [provided by Alliance of Genome Resources, Apr 2022]

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072770655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203403.2. 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
	LURAP1L	NM_203403.2	MANE Select	c.173G>C	p.Ser58Thr	missense	Exon 1 of 2	NP_981948.1	Q8IV03
	LURAP1L-AS1	NR_125775.1		n.243+14732C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LURAP1L	ENST00000319264.4	TSL:1 MANE Select	c.173G>C	p.Ser58Thr	missense	Exon 1 of 2	ENSP00000321026.3	Q8IV03
	LURAP1L	ENST00000489107.1	TSL:2	n.221G>C		non_coding_transcript_exon	Exon 1 of 2
	LURAP1L-AS1	ENST00000417638.1	TSL:3	n.199+14732C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418592 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 702540

African (AFR) AF: 0.0000309 AC: 1 AN: 32330

American (AMR) AF: 0.00 AC: 0 AN: 37272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25466

East Asian (EAS) AF: 0.00 AC: 0 AN: 37066

South Asian (SAS) AF: 0.00 AC: 0 AN: 82704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089988

Other (OTH) AF: 0.00 AC: 0 AN: 58792

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000314 Hom.: 0

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	Benign	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.93
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.062
Sift	Benign	0.39	T
Sift4G	Benign	0.19	T
Vest4		0.12
MVP		0.43
MPC		0.030
ClinPred		0.20	T
GERP RS		3.2
gMVP		0.19
Mutation Taster		=94/6	polymorphism

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: rs1688795485; hg19: chr9-12775887;