chr3-66380635-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015541.3(LRIG1):ā€‹c.2997C>Gā€‹(p.Asn999Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,614,226 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: š‘“ 0.00047 ( 1 hom., cov: 33)
Exomes š‘“: 0.00041 ( 5 hom. )

Consequence

LRIG1
NM_015541.3 missense

Scores

12
5

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.91
Variant links:
Genes affected
LRIG1 (HGNC:17360): (leucine rich repeats and immunoglobulin like domains 1) Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009337217).
BP6
Variant 3-66380635-G-C is Benign according to our data. Variant chr3-66380635-G-C is described in ClinVar as [Benign]. Clinvar id is 3045833.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 72 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRIG1NM_015541.3 linkuse as main transcriptc.2997C>G p.Asn999Lys missense_variant 18/19 ENST00000273261.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRIG1ENST00000273261.8 linkuse as main transcriptc.2997C>G p.Asn999Lys missense_variant 18/191 NM_015541.3 P1Q96JA1-1

Frequencies

GnomAD3 genomes
AF:
0.000460
AC:
70
AN:
152226
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00340
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00147
AC:
369
AN:
250984
Hom.:
4
AF XY:
0.00120
AC XY:
163
AN XY:
135724
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00974
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:
0.000194
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000407
AC:
595
AN:
1461882
Hom.:
5
Cov.:
33
AF XY:
0.000371
AC XY:
270
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.00912
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000473
AC:
72
AN:
152344
Hom.:
1
Cov.:
33
AF XY:
0.000470
AC XY:
35
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000236
Hom.:
0
Bravo
AF:
0.000816
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00120
AC:
146
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

LRIG1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 11, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.94
D
MetaRNN
Benign
0.0093
T;T
MetaSVM
Uncertain
0.13
D
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
1.0
D;D
Vest4
0.84
MutPred
0.27
Gain of ubiquitination at N999 (P = 0.0128);.;
MVP
0.67
MPC
0.17
ClinPred
0.054
T
GERP RS
3.8
Varity_R
0.39
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs140051529; hg19: chr3-66431059; COSMIC: COSV104382678; COSMIC: COSV104382678; API