9-12775821-A-G

Position:

• chr9-12775821-A-G

Variant summary

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

The NM_203403.2(LURAP1L):​c.106A>G​(p.Arg36Gly) 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. 13/18 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LURAP1L NM_203403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.476

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

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=0.059924453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LURAP1L	NM_203403.2	c.106A>G	p.Arg36Gly	missense_variant	1/2	ENST00000319264.4	NP_981948.1
LURAP1L-AS1	NR_125775.1	n.243+14799T>C		intron_variant, non_coding_transcript_variant
LURAP1L	XM_005251443.4	c.106A>G	p.Arg36Gly	missense_variant	1/2		XP_005251500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LURAP1L	ENST00000319264.4	c.106A>G	p.Arg36Gly	missense_variant	1/2	1	NM_203403.2	ENSP00000321026	P1
LURAP1L-AS1	ENST00000417638.1	n.199+14799T>C		intron_variant, non_coding_transcript_variant		3
LURAP1L	ENST00000489107.1	n.154A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453024 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722744

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.106A>G (p.R36G) alteration is located in exon 1 (coding exon 1) of the LURAP1L gene. This alteration results from a A to G substitution at nucleotide position 106, causing the arginine (R) at amino acid position 36 to be replaced by a glycine (G). 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
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.58
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.041
Sift	Benign	0.19	T
Sift4G	Benign	0.096	T
Vest4		0.062
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0275);
MVP		0.16
MPC		0.036
ClinPred		0.020	T
GERP RS		-1.5
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-12775820;