Variant 3-169856752-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024727.4(LRRC31):c.608T>C(p.Ile203Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000124 in 1,607,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

LRRC31
NM_024727.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014887303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC31	NM_024727.4 linkuse as main transcript	c.608T>C	p.Ile203Thr	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.608T>C	p.Ile203Thr	missense_variant	4/9	1	NM_024727.4	P1	Q6UY01-1
LRRC31	ENST00000523069.1 linkuse as main transcript	c.608T>C	p.Ile203Thr	missense_variant	4/9	1			Q6UY01-4
LRRC31	ENST00000264676.9 linkuse as main transcript	c.440T>C	p.Ile147Thr	missense_variant	3/8	2			Q6UY01-2
LRRC31	ENST00000397805.2 linkuse as main transcript	n.675T>C		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.000704

AC:

107

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000479

GnomAD3 exomes

AF:

0.000152

AC:

AN:

244204

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

132590

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000639

AC:

AN:

1455438

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

723860

show subpopulations

Gnomad4 AFR exome

AF:

0.00244

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.000697

AC:

106

AN:

152064

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00251

Gnomad4 AMR

AF:

0.0000655

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:

0.000474

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000880

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000199

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

Aug 02, 2023

The c.608T>C (p.I203T) alteration is located in exon 5 (coding exon 4) of the LRRC31 gene. This alteration results from a T to C substitution at nucleotide position 608, causing the isoleucine (I) at amino acid position 203 to be replaced by a threonine (T). 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

0.32

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.091

T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.10

B;B;.

Vest4

0.48

MVP

0.37

MPC

0.036

ClinPred

0.080

GERP RS

2.4

Varity_R

0.22

gMVP

0.78

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