Variant chr12-12361223-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_058169.6(BORCS5):c.76A>G(p.Lys26Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

BORCS5
NM_058169.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88

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]

BORCS5 links:

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=0.19828328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORCS5	NM_058169.6 linkuse as main transcript	c.76A>G	p.Lys26Glu	missense_variant	2/4	ENST00000314565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORCS5	ENST00000314565.9 linkuse as main transcript	c.76A>G	p.Lys26Glu	missense_variant	2/4	1	NM_058169.6	P1	Q969J3-1
BORCS5	ENST00000298571.6 linkuse as main transcript	c.58+3714A>G		intron_variant		1			Q969J3-2
BORCS5	ENST00000542728.5 linkuse as main transcript	c.19A>G	p.Lys7Glu	missense_variant	2/4	3
BORCS5	ENST00000543990.1 linkuse as main transcript	n.170A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

251480

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000141

AC:

206

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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 submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.76A>G (p.K26E) alteration is located in exon 2 (coding exon 2) of the BORCS5 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the lysine (K) at amino acid position 26 to be replaced by a glutamic acid (E). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0084

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.20

.;T

Polyphen

0.39

.;B

Vest4

0.54

MutPred

0.29

.;Loss of ubiquitination at K26 (P = 0.0023);

MVP

0.50

MPC

0.51

ClinPred

0.087

GERP RS

6.0

Varity_R

0.36

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over