Variant 8-91200637-A-C 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.778A>C(p.Asn260His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 1,303,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.0000023 ( 0 hom. )

Consequence

LRRC69
NM_001129890.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.383

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=0.22064373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC69	NM_001129890.2 linkuse as main transcript	c.778A>C	p.Asn260His	missense_variant	7/8	ENST00000448384.3	NP_001123362.1
LRRC69	NM_001354470.2 linkuse as main transcript	c.310A>C	p.Asn104His	missense_variant	3/4		NP_001341399.1
LRRC69	NR_148895.2 linkuse as main transcript	n.1220A>C		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC69	ENST00000448384.3 linkuse as main transcript	c.778A>C	p.Asn260His	missense_variant	7/8	5	NM_001129890.2	ENSP00000400803	P1	Q6ZNQ3-1
LRRC69	ENST00000343709.7 linkuse as main transcript	c.310A>C	p.Asn104His	missense_variant	3/4	2		ENSP00000343221		Q6ZNQ3-2
LRRC69	ENST00000520099.5 linkuse as main transcript	c.*967A>C		3_prime_UTR_variant, NMD_transcript_variant	9/11	2		ENSP00000428537

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000230

AC:

AN:

1303362

Hom.:

Cov.:

AF XY:

0.00000314

AC XY:

AN XY:

637032

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

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:

0.00

Gnomad4 OTH exome

AF:

0.0000185

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

Feb 10, 2023

The c.778A>C (p.N260H) alteration is located in exon 7 (coding exon 7) of the LRRC69 gene. This alteration results from a A to C substitution at nucleotide position 778, causing the asparagine (N) at amino acid position 260 to be replaced by a histidine (H). 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

0.071

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.3

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.096

Sift

Benign

0.037

D;T

Sift4G

Uncertain

0.039

D;T

Polyphen

1.0

D;D

Vest4

0.36

MutPred

0.48

.;Gain of sheet (P = 0.0266);

MVP

0.11

ClinPred

0.26

GERP RS

1.3

Varity_R

0.040

gMVP

0.069

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