Variant 10-132337566-A-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_030626.3(LRRC27):c.212A>G(p.Gln71Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

LRRC27
NM_030626.3 missense, splice_region

Scores

Splicing: ADA: 0.06462

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

LRRC27 (HGNC:29346): (leucine rich repeat containing 27)

LRRC27 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=0.2737671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC27	NM_030626.3 link	c.212A>G	p.Gln71Arg	missense_variant, splice_region_variant	3/11	ENST00000368614.8	NP_085129.1	Q9C0I9-1A0A140VJN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC27	ENST00000368614.8 link	c.212A>G	p.Gln71Arg	missense_variant, splice_region_variant	3/11	1	NM_030626.3	ENSP00000357603.3		Q9C0I9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

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

Aug 04, 2024

The c.212A>G (p.Q71R) alteration is located in exon 3 (coding exon 2) of the LRRC27 gene. This alteration results from a A to G substitution at nucleotide position 212, causing the glutamine (Q) at amino acid position 71 to be replaced by an arginine (R). 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

0.29

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

.;.;T;T;.

Eigen

Benign

0.058

Eigen_PC

Benign

0.089

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.52

T;T;.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

L;L;L;L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.1

N;.;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.073

T;.;T;T;D

Sift4G

Uncertain

0.043

D;D;T;T;T

Polyphen

0.99

D;P;D;D;P

Vest4

0.38

MutPred

0.39

Gain of catalytic residue at Q71 (P = 0.0254);Gain of catalytic residue at Q71 (P = 0.0254);Gain of catalytic residue at Q71 (P = 0.0254);Gain of catalytic residue at Q71 (P = 0.0254);.;

MVP

0.32

MPC

0.37

ClinPred

0.85

GERP RS

4.7

Varity_R

0.16

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.065

dbscSNV1_RF

Benign

0.38

SpliceAI score (max)

0.040

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