17-46512809-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001006607.3(LRRC37A2):ā€‹c.97C>Gā€‹(p.Leu33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000023 ( 0 hom., cov: 15)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LRRC37A2
NM_001006607.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.193
Variant links:
Genes affected
LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15988559).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC37A2NM_001006607.3 linkuse as main transcriptc.97C>G p.Leu33Val missense_variant 1/14 ENST00000576629.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC37A2ENST00000576629.6 linkuse as main transcriptc.97C>G p.Leu33Val missense_variant 1/145 NM_001006607.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
86010
Hom.:
0
Cov.:
15
FAILED QC
Gnomad AFR
AF:
0.0000609
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
601278
Hom.:
0
Cov.:
4
AF XY:
0.00
AC XY:
0
AN XY:
299984
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000233
AC:
2
AN:
86010
Hom.:
0
Cov.:
15
AF XY:
0.00
AC XY:
0
AN XY:
42498
show subpopulations
Gnomad4 AFR
AF:
0.0000609
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:
0.00
Gnomad4 OTH
AF:
0.00

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 GeneticsJan 23, 2023The c.97C>G (p.L33V) alteration is located in exon 1 (coding exon 1) of the LRRC37A2 gene. This alteration results from a C to G substitution at nucleotide position 97, causing the leucine (L) at amino acid position 33 to be replaced by a valine (V). 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
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
1.8
DANN
Benign
0.89
DEOGEN2
Benign
0.014
T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.76
.;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.3
L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.8
.;N
REVEL
Benign
0.079
Sift
Benign
0.32
.;T
Sift4G
Benign
0.13
T;T
Polyphen
0.97
D;D
Vest4
0.21
MutPred
0.37
Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);
MVP
0.061
ClinPred
0.15
T
GERP RS
-0.97
Varity_R
0.058
gMVP
0.047

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.

Other links and lift over

dbSNP: rs1319456896; hg19: chr17-44590175; API