Variant 3-169856736-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024727.4(LRRC31):c.624C>G(p.Cys208Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,597,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

LRRC31
NM_024727.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.135

Variant links:

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

LRRC31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC31	NM_024727.4 linkuse as main transcript	c.624C>G	p.Cys208Trp	missense_variant	4/9	ENST00000316428.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC31	ENST00000316428.10 linkuse as main transcript	c.624C>G	p.Cys208Trp	missense_variant	4/9	1	NM_024727.4	P1	Q6UY01-1
LRRC31	ENST00000523069.1 linkuse as main transcript	c.624C>G	p.Cys208Trp	missense_variant	4/9	1			Q6UY01-4
LRRC31	ENST00000264676.9 linkuse as main transcript	c.456C>G	p.Cys152Trp	missense_variant	3/8	2			Q6UY01-2
LRRC31	ENST00000397805.2 linkuse as main transcript	n.691C>G		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151520

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000837

AC:

AN:

238830

Hom.:

AF XY:

0.00000771

AC XY:

AN XY:

129630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1445622

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

718068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

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:

0.00000272

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151520

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73998

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000828

AC:

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

Dec 30, 2023

The c.624C>G (p.C208W) alteration is located in exon 5 (coding exon 4) of the LRRC31 gene. This alteration results from a C to G substitution at nucleotide position 624, causing the cysteine (C) at amino acid position 208 to be replaced by a tryptophan (W). 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.12

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.21

T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.7

M;.;M

MutationTaster

Benign

0.73

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-9.2

D;D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.96

MutPred

0.79

Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);

MVP

0.45

MPC

0.25

ClinPred

0.99

GERP RS

-3.8

Varity_R

0.84

gMVP

0.80

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