Variant 3-169840011-T-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 ENST00000316428.10(LRRC31):c.1630A>C(p.Ile544Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,194 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: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LRRC31
ENST00000316428.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00400

Variant links:

Genes affected

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

LRRC31 links:

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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=0.035874784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC31	NM_024727.4 linkuse as main transcript	c.1630A>C	p.Ile544Leu	missense_variant	9/9	ENST00000316428.10	NP_079003.2	Q6UY01-1A0A384N629

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC31	ENST00000316428.10 linkuse as main transcript	c.1630A>C	p.Ile544Leu	missense_variant	9/9	1	NM_024727.4	ENSP00000325978.5	Q6UY01-1
LRRC31	ENST00000523069 linkuse as main transcript	c.*316A>C		3_prime_UTR_variant	9/9	1		ENSP00000429145.1	Q6UY01-4
LRRC31	ENST00000264676.9 linkuse as main transcript	c.1462A>C	p.Ile488Leu	missense_variant	8/8	2		ENSP00000264676.5	Q6UY01-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000924

AC:

AN:

249010

Hom.:

AF XY:

0.0000814

AC XY:

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000610

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:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461194

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000516

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.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000828

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

Jan 26, 2022

The c.1630A>C (p.I544L) alteration is located in exon 10 (coding exon 9) of the LRRC31 gene. This alteration results from a A to C substitution at nucleotide position 1630, causing the isoleucine (I) at amino acid position 544 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.5

DANN

Benign

0.90

DEOGEN2

Benign

0.0041

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.061

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.0060

B;P

Vest4

0.18

MutPred

0.34

Gain of glycosylation at S543 (P = 0.0245);.;

MVP

0.13

MPC

0.035

ClinPred

0.055

GERP RS

-0.46

Varity_R

0.073

gMVP

0.26

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