chr17-46512917-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001006607.3(LRRC37A2):​c.205C>T​(p.Arg69Trp) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 2 hom., cov: 16)
Exomes 𝑓: 0.000056 ( 3 hom. )
Failed GnomAD Quality Control

Consequence

LRRC37A2
NM_001006607.3 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.218
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.018391252).
BP6
Variant 17-46512917-C-T is Benign according to our data. Variant chr17-46512917-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2511250.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC37A2NM_001006607.3 linkuse as main transcriptc.205C>T p.Arg69Trp missense_variant 1/14 ENST00000576629.6 NP_001006608.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC37A2ENST00000576629.6 linkuse as main transcriptc.205C>T p.Arg69Trp missense_variant 1/145 NM_001006607.3 ENSP00000459551 P1

Frequencies

GnomAD3 genomes
AF:
0.000246
AC:
22
AN:
89580
Hom.:
2
Cov.:
16
show subpopulations
Gnomad AFR
AF:
0.000600
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000230
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: AS_VQSR
AF:
0.0000562
AC:
40
AN:
712028
Hom.:
3
Cov.:
5
AF XY:
0.0000486
AC XY:
17
AN XY:
350054
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
Gnomad4 AMR exome
AF:
0.0000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000285
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.000193
GnomAD4 genome
AF:
0.000245
AC:
22
AN:
89694
Hom.:
2
Cov.:
16
AF XY:
0.000226
AC XY:
10
AN XY:
44336
show subpopulations
Gnomad4 AFR
AF:
0.000598
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000230
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
ESP6500AA
AF:
0.00126
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000133
AC:
10

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 GeneticsApr 13, 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
0.069
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
6.2
DANN
Benign
0.88
DEOGEN2
Benign
0.00074
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0058
N
LIST_S2
Benign
0.55
.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.018
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-2.0
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
3.5
.;N
REVEL
Benign
0.068
Sift
Uncertain
0.029
.;D
Sift4G
Benign
0.13
T;T
Polyphen
0.0010
B;B
Vest4
0.15
MVP
0.040
ClinPred
0.040
T
GERP RS
-0.14
Varity_R
0.036
gMVP
0.061

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: rs373973615; hg19: chr17-44590283; API