Variant 8-91102708-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001129890.2(LRRC69):c.47C>T(p.Thr16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000556 in 1,551,380 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 2 hom. )

Consequence

LRRC69
NM_001129890.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

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_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08230716).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC69	NM_001129890.2 linkuse as main transcript	c.47C>T	p.Thr16Met	missense_variant	1/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2 linkuse as main transcript	c.47C>T	p.Thr16Met	missense_variant	1/4		NP_001341399.1
LRRC69	NR_148895.2 linkuse as main transcript	n.90C>T		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3 linkuse as main transcript	c.47C>T	p.Thr16Met	missense_variant	1/8	5	NM_001129890.2	ENSP00000400803	P1	Q6ZNQ3-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000351

AC:

AN:

156794

Hom.:

AF XY:

0.000434

AC XY:

AN XY:

82908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000572

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000559

Gnomad OTH exome

AF:

0.000910

GnomAD4 exome

AF:

0.000578

AC:

809

AN:

1399110

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

407

AN XY:

690050

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000733

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000650

Gnomad4 OTH exome

AF:

0.000672

GnomAD4 genome

AF:

0.000355

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000604

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000355

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 01, 2024

The c.47C>T (p.T16M) alteration is located in exon 1 (coding exon 1) of the LRRC69 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the threonine (T) at amino acid position 16 to be replaced by a methionine (M). 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

0.24

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.013

.;.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.2

.;M;M

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.0

D;N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;T;D

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

1.0

.;D;D

Vest4

0.60, 0.59

MVP

0.28

ClinPred

0.18

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.094

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