chr9-12775893-A-T

Position:

• chr9-12775893-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000319264.4(LURAP1L):​c.178A>T​(p.Ser60Cys) 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: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LURAP1L ENST00000319264.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.593

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3814066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LURAP1L	NM_203403.2	c.178A>T	p.Ser60Cys	missense_variant	1/2	ENST00000319264.4	NP_981948.1
LURAP1L-AS1	NR_125775.1	n.243+14727T>A		intron_variant, non_coding_transcript_variant
LURAP1L	XM_005251443.4	c.178A>T	p.Ser60Cys	missense_variant	1/2		XP_005251500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LURAP1L	ENST00000319264.4	c.178A>T	p.Ser60Cys	missense_variant	1/2	1	NM_203403.2	ENSP00000321026	P1
LURAP1L-AS1	ENST00000417638.1	n.199+14727T>A		intron_variant, non_coding_transcript_variant		3
LURAP1L	ENST00000489107.1	n.226A>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000283 AC: 4 AN: 1413608 Hom.: 0 Cov.: 34 AF XY: 0.00000428 AC XY: 3 AN XY: 700416

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: 0.00000276

Gnomad4 OTH exome AF: 0.0000171

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

Jul 09, 2021

The c.178A>T (p.S60C) alteration is located in exon 1 (coding exon 1) of the LURAP1L gene. This alteration results from a A to T substitution at nucleotide position 178, causing the serine (S) at amino acid position 60 to be replaced by a cysteine (C). 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	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.96
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.56	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.95	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.053
Sift	Benign	0.24	T
Sift4G	Uncertain	0.0080	D
Vest4		0.28
MVP		0.65
MPC		0.19
ClinPred		0.64	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs1403755230; hg19: chr9-12775892;