chr17-46297471-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014834.4(LRRC37A):ā€‹c.2338G>Cā€‹(p.Val780Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000060 ( 3 hom., cov: 18)
Exomes š‘“: 0.00012 ( 40 hom. )
Failed GnomAD Quality Control

Consequence

LRRC37A
NM_014834.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.200
Variant links:
Genes affected
LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) 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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0072587132).
BP6
Variant 17-46297471-G-C is Benign according to our data. Variant chr17-46297471-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3120581.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC37ANM_014834.4 linkuse as main transcriptc.2338G>C p.Val780Leu missense_variant 1/14 ENST00000320254.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC37AENST00000320254.5 linkuse as main transcriptc.2338G>C p.Val780Leu missense_variant 1/141 NM_014834.4 P2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
9
AN:
116400
Hom.:
4
Cov.:
18
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00671
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:
0.00129
AC:
65
AN:
50466
Hom.:
25
AF XY:
0.000943
AC XY:
24
AN XY:
25444
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0128
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000551
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000119
AC:
145
AN:
1220840
Hom.:
40
Cov.:
26
AF XY:
0.000110
AC XY:
68
AN XY:
615498
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00543
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000108
Gnomad4 OTH exome
AF:
0.0000972
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000601
AC:
7
AN:
116486
Hom.:
3
Cov.:
18
AF XY:
0.0000725
AC XY:
4
AN XY:
55152
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00522
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0
Bravo
AF:
0.000102

ClinVar

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

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
1.4
DANN
Benign
0.81
DEOGEN2
Benign
0.0094
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0017
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.0073
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
.;M
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.039
Sift
Benign
0.13
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.0
.;B
Vest4
0.23
MutPred
0.27
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.068
ClinPred
0.036
T
GERP RS
-4.1
Varity_R
0.079
gMVP
0.049

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: rs557815137; hg19: chr17-44374837; API