dbSNP rs710415: LRRC23:p.Glu276Ala (chr12-6913959-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000323702.9(LRRC23):c.827A>C(p.Glu276Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC23
ENST00000323702.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0910

Publications

48 publications found

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:

ENO2 (HGNC:3353): (enolase 2) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates. [provided by RefSeq, Jul 2008]

ENO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0629012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000323702.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRRC23	NM_001135217.2	MANE Select	c.*93A>C		3_prime_UTR	Exon 8 of 8	NP_001128689.1
LRRC23	NM_006992.4		c.827A>C	p.Glu276Ala	missense	Exon 7 of 7	NP_008923.1
LRRC23	NM_201650.3		c.*93A>C		3_prime_UTR	Exon 8 of 8	NP_964013.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRRC23	ENST00000323702.9	TSL:1	c.827A>C	p.Glu276Ala	missense	Exon 7 of 7	ENSP00000317464.5
LRRC23	ENST00000429740.1	TSL:1	c.559A>C	p.Asn187His	missense	Exon 4 of 4	ENSP00000397192.1
LRRC23	ENST00000443597.7	TSL:1 MANE Select	c.*93A>C		3_prime_UTR	Exon 8 of 8	ENSP00000390932.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727140

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111830

Other (OTH)

AF:

0.00

AC:

AN:

60380

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.1

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.26

M_CAP

Benign

0.0047

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

PhyloP100

-0.091

PROVEAN

Benign

-0.48

REVEL

Benign

0.049

Sift

Benign

0.28

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.063

MutPred

0.37

Gain of catalytic residue at H271 (P = 0.0244)

MVP

0.17

ClinPred

0.072

GERP RS

-0.78

PromoterAI

0.0037

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over