Variant 8-91124596-G-A 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_001129890.2(LRRC69):c.287G>A(p.Cys96Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,388,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

LRRC69
NM_001129890.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.377

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:

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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=0.07701716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC69	NM_001129890.2 linkuse as main transcript	c.287G>A	p.Cys96Tyr	missense_variant	2/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2 linkuse as main transcript	c.183+21752G>A		intron_variant			NP_001341399.1
LRRC69	NR_148895.2 linkuse as main transcript	n.556-2492G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3 linkuse as main transcript	c.287G>A	p.Cys96Tyr	missense_variant	2/8	5	NM_001129890.2	ENSP00000400803	P1	Q6ZNQ3-1
LRRC69	ENST00000343709.7 linkuse as main transcript	c.183+21752G>A		intron_variant		2		ENSP00000343221		Q6ZNQ3-2
LRRC69	ENST00000522144.1 linkuse as main transcript	n.228G>A		non_coding_transcript_exon_variant	2/2	2
LRRC69	ENST00000520099.5 linkuse as main transcript	c.*303-2492G>A		intron_variant, NMD_transcript_variant		2		ENSP00000428537

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1388554

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684804

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:

0.00000372

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

Mar 22, 2022

The c.287G>A (p.C96Y) alteration is located in exon 2 (coding exon 2) of the LRRC69 gene. This alteration results from a G to A substitution at nucleotide position 287, causing the cysteine (C) at amino acid position 96 to be replaced by a tyrosine (Y). 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

0.082

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.5

DANN

Benign

0.35

DEOGEN2

Benign

0.021

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.51

M_CAP

Benign

0.0080

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.019

Sift

Benign

0.17

Sift4G

Benign

0.31

Polyphen

0.34

Vest4

0.20

MutPred

0.34

Gain of catalytic residue at P100 (P = 0.0669);

MVP

0.048

ClinPred

0.15

GERP RS

-4.3

Varity_R

0.12

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