Variant 13-46553434-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164211.2(LRCH1):c.38C>T(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

LRCH1
NM_001164211.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

LRCH1 (HGNC:20309): (leucine rich repeats and calponin homology domain containing 1) This gene encodes a protein with a leucine-rich repeat and a calponin homology domain. Polymorphism in this gene may be associated with susceptibililty to knee osteoarthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2010]

LRCH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14067754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCH1	NM_001164211.2 linkuse as main transcript	c.38C>T	p.Pro13Leu	missense_variant	1/20	ENST00000389797.8	NP_001157683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH1	ENST00000389797.8 linkuse as main transcript	c.38C>T	p.Pro13Leu	missense_variant	1/20	1	NM_001164211.2	ENSP00000374447		Q9Y2L9-3
LRCH1	ENST00000389798.7 linkuse as main transcript	c.38C>T	p.Pro13Leu	missense_variant	1/19	1		ENSP00000374448	A1	Q9Y2L9-1
LRCH1	ENST00000311191.10 linkuse as main transcript	c.38C>T	p.Pro13Leu	missense_variant	1/19	1		ENSP00000308493	P3	Q9Y2L9-2
LRCH1	ENST00000443945.6 linkuse as main transcript	n.265C>T		non_coding_transcript_exon_variant	1/13	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1396574

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688846

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:

9.27e-7

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 27, 2022

The c.38C>T (p.P13L) alteration is located in exon 1 (coding exon 1) of the LRCH1 gene. This alteration results from a C to T substitution at nucleotide position 38, causing the proline (P) at amino acid position 13 to be replaced by a leucine (L). 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

0.31

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0044

.;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.84

T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.030

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0010

B;B;.

Vest4

0.11

MutPred

0.35

Gain of catalytic residue at V17 (P = 0.0193);Gain of catalytic residue at V17 (P = 0.0193);Gain of catalytic residue at V17 (P = 0.0193);

MVP

0.13

MPC

0.42

ClinPred

0.61

GERP RS

3.2

Varity_R

0.055

gMVP

0.19

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over