Variant 8-91135699-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001129890.2(LRRC69):c.611T>G(p.Leu204Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000356 in 1,462,368 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: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

LRRC69
NM_001129890.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

Variant links:

Genes affected

LRRC69 (HGNC:34303): (leucine rich repeat containing 69) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

LRRC69 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC69	NM_001129890.2 linkuse as main transcript	c.611T>G	p.Leu204Arg	missense_variant	5/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2 linkuse as main transcript	c.183+32855T>G		intron_variant			NP_001341399.1
LRRC69	NR_148895.2 linkuse as main transcript	n.1053T>G		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3 linkuse as main transcript	c.611T>G	p.Leu204Arg	missense_variant	5/8	5	NM_001129890.2	ENSP00000400803	P1	Q6ZNQ3-1
LRRC69	ENST00000343709.7 linkuse as main transcript	c.183+32855T>G		intron_variant		2		ENSP00000343221		Q6ZNQ3-2
LRRC69	ENST00000521519.1 linkuse as main transcript	n.19T>G		non_coding_transcript_exon_variant	1/2	5
LRRC69	ENST00000520099.5 linkuse as main transcript	c.*800T>G		3_prime_UTR_variant, NMD_transcript_variant	7/11	2		ENSP00000428537

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000298

AC:

AN:

1310312

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

645752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000398

Gnomad4 SAS exome

AF:

0.0000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.0000982

Asia WGS

AF:

0.000578

AC:

AN:

3476

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

Oct 10, 2023

The c.611T>G (p.L204R) alteration is located in exon 5 (coding exon 5) of the LRRC69 gene. This alteration results from a T to G substitution at nucleotide position 611, causing the leucine (L) at amino acid position 204 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

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.40

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

4.5

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.4

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.89

MVP

0.57

ClinPred

1.0

GERP RS

5.8

Varity_R

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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