Variant 8-91127095-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001129890.2(LRRC69):c.318A>T(p.Leu106Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,395,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

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: 0.792

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 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=0.3311839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC69	NM_001129890.2 linkuse as main transcript	c.318A>T	p.Leu106Phe	missense_variant	3/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2 linkuse as main transcript	c.183+24251A>T		intron_variant			NP_001341399.1
LRRC69	NR_148895.2 linkuse as main transcript	n.563A>T		non_coding_transcript_exon_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3 linkuse as main transcript	c.318A>T	p.Leu106Phe	missense_variant	3/8	5	NM_001129890.2	ENSP00000400803	P1	Q6ZNQ3-1
LRRC69	ENST00000343709.7 linkuse as main transcript	c.183+24251A>T		intron_variant		2		ENSP00000343221		Q6ZNQ3-2
LRRC69	ENST00000520099.5 linkuse as main transcript	c.*310A>T		3_prime_UTR_variant, NMD_transcript_variant	3/11	2		ENSP00000428537

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000268

AC:

AN:

149154

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000445

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000513

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1395016

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

688136

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:

0.0000381

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jun 05, 2023

The c.318A>T (p.L106F) alteration is located in exon 3 (coding exon 3) of the LRRC69 gene. This alteration results from a A to T substitution at nucleotide position 318, causing the leucine (L) at amino acid position 106 to be replaced by a phenylalanine (F). 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

-0.11

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.57

M_CAP

Benign

0.027

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.84

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.84

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.29

Sift

Uncertain

0.0080

Sift4G

Benign

0.080

Polyphen

0.98

Vest4

0.44

MutPred

0.56

Gain of helix (P = 0.0325);

MVP

0.10

ClinPred

0.54

GERP RS

3.3

Varity_R

0.24

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