Variant 8-91189570-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001129890.2(LRRC69):c.700T>A(p.Phe234Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,551,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

LRRC69
NM_001129890.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.345

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050146848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC69	NM_001129890.2 linkuse as main transcript	c.700T>A	p.Phe234Ile	missense_variant	6/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2 linkuse as main transcript	c.232T>A	p.Phe78Ile	missense_variant	2/4		NP_001341399.1
LRRC69	NR_148895.2 linkuse as main transcript	n.1142T>A		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3 linkuse as main transcript	c.700T>A	p.Phe234Ile	missense_variant	6/8	5	NM_001129890.2	ENSP00000400803	P1	Q6ZNQ3-1
LRRC69	ENST00000343709.7 linkuse as main transcript	c.232T>A	p.Phe78Ile	missense_variant	2/4	2		ENSP00000343221		Q6ZNQ3-2
LRRC69	ENST00000520099.5 linkuse as main transcript	c.*889T>A		3_prime_UTR_variant, NMD_transcript_variant	8/11	2		ENSP00000428537

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000134

AC:

AN:

157218

Hom.:

AF XY:

0.0000962

AC XY:

AN XY:

83164

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000356

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000200

AC:

280

AN:

1398918

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

129

AN XY:

689982

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

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:

0.000101

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000803

AC:

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

Dec 07, 2021

The c.700T>A (p.F234I) alteration is located in exon 6 (coding exon 6) of the LRRC69 gene. This alteration results from a T to A substitution at nucleotide position 700, causing the phenylalanine (F) at amino acid position 234 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0036

.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.75

N;N

REVEL

Benign

0.040

Sift

Benign

0.24

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.074

B;B

Vest4

0.25

MVP

0.040

ClinPred

0.056

GERP RS

0.31

Varity_R

0.055

gMVP

0.041

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