Variant 12-6909917-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001135217.2(LRRC23):c.649G>A(p.Gly217Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,354 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: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LRRC23
NM_001135217.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC23	NM_001135217.2 linkuse as main transcript	c.649G>A	p.Gly217Ser	missense_variant	6/8	ENST00000443597.7	NP_001128689.1	Q53EV4-1A8K8K2
LRRC23	NM_201650.3 linkuse as main transcript	c.649G>A	p.Gly217Ser	missense_variant	6/8		NP_964013.1	Q53EV4-1A8K8K2
LRRC23	NM_006992.4 linkuse as main transcript	c.649G>A	p.Gly217Ser	missense_variant	6/7		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.649G>A	p.Gly217Ser	missense_variant	6/8	1	NM_001135217.2	ENSP00000390932.2		Q53EV4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250852

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135598

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461354

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727006

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000756

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

Jun 28, 2023

The c.649G>A (p.G217S) alteration is located in exon 6 (coding exon 5) of the LRRC23 gene. This alteration results from a G to A substitution at nucleotide position 649, causing the glycine (G) at amino acid position 217 to be replaced by a serine (S). 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

0.33

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.080

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.82

L;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.1

D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.054

T;D;T

Sift4G

Benign

0.16

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.68

MutPred

0.42

Gain of phosphorylation at G217 (P = 0.0545);Gain of phosphorylation at G217 (P = 0.0545);Gain of phosphorylation at G217 (P = 0.0545);

MVP

0.73

MPC

0.62

ClinPred

0.96

GERP RS

4.9

Varity_R

0.47

gMVP

0.56

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