NM_017622.3:c.326G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017622.3(BORCS6):​c.326G>C​(p.Arg109Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,583,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000051 ( 1 hom. )

Consequence

BORCS6
NM_017622.3 missense

Scores

17

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.145
Variant links:
Genes affected
BORCS6 (HGNC:25939): (BLOC-1 related complex subunit 6) Enables identical protein binding activity. Involved in lysosome localization. Part of BORC complex. [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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017098755).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BORCS6NM_017622.3 linkc.326G>C p.Arg109Pro missense_variant Exon 1 of 1 ENST00000389017.6 NP_060092.2 Q96GS4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BORCS6ENST00000389017.6 linkc.326G>C p.Arg109Pro missense_variant Exon 1 of 1 6 NM_017622.3 ENSP00000373669.4 Q96GS4
ENSG00000279152ENST00000622992.1 linkn.*127C>G downstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000912
AC:
17
AN:
186324
Hom.:
0
AF XY:
0.000115
AC XY:
12
AN XY:
104238
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000618
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000510
AC:
73
AN:
1431360
Hom.:
1
Cov.:
34
AF XY:
0.0000717
AC XY:
51
AN XY:
710996
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000831
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.08e-7
Gnomad4 OTH exome
AF:
0.0000337
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152274
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.000103
AC:
12

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Fraser syndrome 3 Uncertain:1
-
Department of Molecular Biology and Genetics, Acibadem University
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
10
DANN
Benign
0.93
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.017
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
0.050
N
REVEL
Benign
0.030
Sift
Benign
0.15
T
Sift4G
Benign
0.20
T
Polyphen
0.91
P
Vest4
0.078
MutPred
0.21
Loss of stability (P = 0.0259);
MVP
0.088
ClinPred
0.036
T
GERP RS
2.0
Varity_R
0.18
gMVP
0.12

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: rs561853521; hg19: chr17-8093133; API