Variant 3-194359596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130830.5(LRRC15):c.1448G>A(p.Ser483Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LRRC15
NM_130830.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0230

Variant links:

Genes affected

LRRC15 (HGNC:20818): (leucine rich repeat containing 15) Enables collagen binding activity; fibronectin binding activity; and laminin binding activity. Involved in negative regulation of protein localization to plasma membrane; positive regulation of cell migration; and receptor-mediated virion attachment to host cell. Located in extracellular exosome. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

LRRC15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07481021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC15	NM_130830.5 linkuse as main transcript	c.1448G>A	p.Ser483Asn	missense_variant	2/2	ENST00000347624.4	NP_570843.2	Q8TF66-1B3KWI4
LRRC15	NM_001135057.3 linkuse as main transcript	c.1466G>A	p.Ser489Asn	missense_variant	3/3		NP_001128529.2	Q8TF66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC15	ENST00000347624.4 linkuse as main transcript	c.1448G>A	p.Ser483Asn	missense_variant	2/2	1	NM_130830.5	ENSP00000306276.4		Q8TF66-1
LRRC15	ENST00000428839.1 linkuse as main transcript	c.1466G>A	p.Ser489Asn	missense_variant	3/3	1		ENSP00000413707.1		Q8TF66-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249956

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.1466G>A (p.S489N) alteration is located in exon 3 (coding exon 2) of the LRRC15 gene. This alteration results from a G to A substitution at nucleotide position 1466, causing the serine (S) at amino acid position 489 to be replaced by an asparagine (N). 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

0.083

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.8

DANN

Benign

0.86

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.037

Sift

Benign

0.030

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.090

B;B

Vest4

0.13

MutPred

0.32

Loss of glycosylation at S483 (P = 0.003);.;

MVP

0.33

ClinPred

0.045

GERP RS

-0.010

Varity_R

0.057

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over