chr8-91127127-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001129890.2(LRRC69):ā€‹c.350A>Gā€‹(p.Asn117Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000245 in 1,548,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.000026 ( 0 hom. )

Consequence

LRRC69
NM_001129890.2 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.35
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC69NM_001129890.2 linkuse as main transcriptc.350A>G p.Asn117Ser missense_variant 3/8 ENST00000448384.3 NP_001123362.1
LRRC69NM_001354470.2 linkuse as main transcriptc.183+24283A>G intron_variant NP_001341399.1
LRRC69NR_148895.2 linkuse as main transcriptn.595A>G non_coding_transcript_exon_variant 3/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC69ENST00000448384.3 linkuse as main transcriptc.350A>G p.Asn117Ser missense_variant 3/85 NM_001129890.2 ENSP00000400803 P1Q6ZNQ3-1
LRRC69ENST00000343709.7 linkuse as main transcriptc.183+24283A>G intron_variant 2 ENSP00000343221 Q6ZNQ3-2
LRRC69ENST00000520099.5 linkuse as main transcriptc.*342A>G 3_prime_UTR_variant, NMD_transcript_variant 3/112 ENSP00000428537

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152054
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000139
AC:
21
AN:
150934
Hom.:
0
AF XY:
0.000125
AC XY:
10
AN XY:
80234
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000818
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:
0.0000340
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000265
AC:
37
AN:
1396682
Hom.:
0
Cov.:
30
AF XY:
0.0000232
AC XY:
16
AN XY:
688956
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000637
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000121
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152054
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000314
AC:
1

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 submitterclinical testingAmbry GeneticsJul 20, 2021The c.350A>G (p.N117S) alteration is located in exon 3 (coding exon 3) of the LRRC69 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the asparagine (N) at amino acid position 117 to be replaced by a serine (S). 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
Uncertain
0.55
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.040
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.33
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.15
T
Polyphen
1.0
D
Vest4
0.74
MVP
0.21
ClinPred
0.73
D
GERP RS
5.9
Varity_R
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs377430717; hg19: chr8-92139355; API