Variant 3-169851748-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024727.4(LRRC31):c.1030G>A(p.Asp344Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LRRC31
NM_024727.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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 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=0.35536656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC31	NM_024727.4 linkuse as main transcript	c.1030G>A	p.Asp344Asn	missense_variant	7/9	ENST00000316428.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC31	ENST00000316428.10 linkuse as main transcript	c.1030G>A	p.Asp344Asn	missense_variant	7/9	1	NM_024727.4	P1	Q6UY01-1
LRRC31	ENST00000523069.1 linkuse as main transcript	c.1030G>A	p.Asp344Asn	missense_variant	7/9	1			Q6UY01-4
LRRC31	ENST00000264676.9 linkuse as main transcript	c.862G>A	p.Asp288Asn	missense_variant	6/8	2			Q6UY01-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249558

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727232

show subpopulations

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

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

Jul 12, 2022

The c.1030G>A (p.D344N) alteration is located in exon 8 (coding exon 7) of the LRRC31 gene. This alteration results from a G to A substitution at nucleotide position 1030, causing the aspartic acid (D) at amino acid position 344 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

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;.;.

Eigen

Benign

-0.029

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;.;L

MutationTaster

Benign

0.88

D;D;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.81

P;P;.

Vest4

0.30

MutPred

0.62

Gain of glycosylation at S346 (P = 0.0575);.;Gain of glycosylation at S346 (P = 0.0575);

MVP

0.69

MPC

0.14

ClinPred

0.93

GERP RS

3.0

Varity_R

0.12

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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