Variant 12-6905860-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001135217.2(LRRC23):c.142C>G(p.Leu48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

LRRC23
NM_001135217.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

LRRC23 (HGNC:19138): (leucine rich repeat containing 23) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRRC23 links:

LRRC23 (HGNC:):

LRRC23 links:

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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=0.37067774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC23	NM_001135217.2 linkuse as main transcript	c.142C>G	p.Leu48Val	missense_variant	3/8	ENST00000443597.7	NP_001128689.1	Q53EV4-1A8K8K2
LRRC23	NM_201650.3 linkuse as main transcript	c.142C>G	p.Leu48Val	missense_variant	3/8		NP_964013.1	Q53EV4-1A8K8K2
LRRC23	NM_006992.4 linkuse as main transcript	c.142C>G	p.Leu48Val	missense_variant	3/7		NP_008923.1	Q53EV4-2A8K8K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC23	ENST00000443597.7 linkuse as main transcript	c.142C>G	p.Leu48Val	missense_variant	3/8	1	NM_001135217.2	ENSP00000390932.2		Q53EV4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251458

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

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

May 04, 2023

The c.142C>G (p.L48V) alteration is located in exon 3 (coding exon 2) of the LRRC23 gene. This alteration results from a C to G substitution at nucleotide position 142, causing the leucine (L) at amino acid position 48 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

.;T;.;.;T;T;T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;.;T;T;T;T;T;.

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.37

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.9

.;M;.;M;M;.;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

N;N;.;N;N;D;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0090

D;D;.;D;D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D;D;D;D

Polyphen

1.0

D;P;D;D;P;.;.;D

Vest4

0.53

MutPred

0.40

Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);Gain of catalytic residue at L48 (P = 0);

MVP

0.71

MPC

0.53

ClinPred

0.85

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.13

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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