Variant 12-6906438-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_001135217.2(LRRC23):c.266C>T(p.Ser89Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,818 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: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LRRC23
NM_001135217.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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=0.36176884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC23	NM_001135217.2 linkuse as main transcript	c.266C>T	p.Ser89Phe	missense_variant	4/8	ENST00000443597.7	NP_001128689.1	Q53EV4-1A8K8K2
LRRC23	NM_201650.3 linkuse as main transcript	c.266C>T	p.Ser89Phe	missense_variant	4/8		NP_964013.1	Q53EV4-1A8K8K2
LRRC23	NM_006992.4 linkuse as main transcript	c.266C>T	p.Ser89Phe	missense_variant	4/7		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.266C>T	p.Ser89Phe	missense_variant	4/8	1	NM_001135217.2	ENSP00000390932.2		Q53EV4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251334

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Apr 26, 2024

The c.266C>T (p.S89F) alteration is located in exon 4 (coding exon 3) of the LRRC23 gene. This alteration results from a C to T substitution at nucleotide position 266, causing the serine (S) at amino acid position 89 to be replaced by a phenylalanine (F). 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

-0.18

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

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

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

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

M_CAP

Benign

0.021

MetaRNN

Benign

0.36

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

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.5

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

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.0

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

REVEL

Benign

0.18

Sift

Benign

0.052

T;T;.;D;T;D;D;D

Sift4G

Uncertain

0.016

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

Polyphen

0.61

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

Vest4

0.43

MutPred

0.56

Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);Gain of catalytic residue at R94 (P = 0.0112);

MVP

0.63

MPC

0.47

ClinPred

0.78

GERP RS

5.9

Varity_R

0.22

gMVP

0.57

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