chr12-12465759-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_058169.6(BORCS5):​c.574C>T​(p.Arg192Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R192H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

BORCS5
NM_058169.6 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
Variant links:
Genes affected
BORCS5 (HGNC:17950): (BLOC-1 related complex subunit 5) Involved in lysosome localization and organelle transport along microtubule. Located in cytoplasmic side of lysosomal membrane and plasma membrane. Is intrinsic component of membrane. Part of BORC complex. Colocalizes with plus-end kinesin complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25367856).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BORCS5NM_058169.6 linkuse as main transcriptc.574C>T p.Arg192Cys missense_variant 4/4 ENST00000314565.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BORCS5ENST00000314565.9 linkuse as main transcriptc.574C>T p.Arg192Cys missense_variant 4/41 NM_058169.6 P1Q969J3-1
BORCS5ENST00000298571.6 linkuse as main transcriptc.430C>T p.Arg144Cys missense_variant 3/31 Q969J3-2
BORCS5ENST00000542728.5 linkuse as main transcriptc.517C>T p.Arg173Cys missense_variant 4/43

Frequencies

GnomAD3 genomes
AF:
0.0000985
AC:
15
AN:
152262
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000531
AC:
13
AN:
244968
Hom.:
0
AF XY:
0.0000525
AC XY:
7
AN XY:
133438
show subpopulations
Gnomad AFR exome
AF:
0.000456
Gnomad AMR exome
AF:
0.000116
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:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1460496
Hom.:
0
Cov.:
34
AF XY:
0.0000220
AC XY:
16
AN XY:
726578
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.0000895
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:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152262
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.0000654
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
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000495
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsJun 11, 2021The c.574C>T (p.R192C) alteration is located in exon 4 (coding exon 4) of the BORCS5 gene. This alteration results from a C to T substitution at nucleotide position 574, causing the arginine (R) at amino acid position 192 to be replaced by a cysteine (C). 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
0.12
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T;T;.
Eigen
Benign
0.19
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.80
D
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-0.74
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0010
.;D;D
Polyphen
0.99, 0.89
.;D;P
Vest4
0.63
MVP
0.62
MPC
1.1
ClinPred
0.15
T
GERP RS
5.7
Varity_R
0.18
gMVP
0.61

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: rs139969054; hg19: chr12-12618693; COSMIC: COSV53801299; API