Variant chr12-12465757-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_058169.6(BORCS5):c.572A>G(p.Asp191Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000651 in 1,612,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. D191N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 1 hom. )

Consequence

BORCS5
NM_058169.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

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 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=0.021183103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORCS5	NM_058169.6 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	4/4	ENST00000314565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORCS5	ENST00000314565.9 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	4/4	1	NM_058169.6	P1	Q969J3-1
BORCS5	ENST00000298571.6 linkuse as main transcript	c.428A>G	p.Asp143Gly	missense_variant	3/3	1			Q969J3-2
BORCS5	ENST00000542728.5 linkuse as main transcript	c.515A>G	p.Asp172Gly	missense_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000570

AC:

AN:

245732

Hom.:

AF XY:

0.0000449

AC XY:

AN XY:

133776

show subpopulations

Gnomad AFR exome

AF:

0.000842

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1460658

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000381

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000476

Hom.:

Bravo

AF:

0.000533

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

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

Aug 08, 2023

The c.572A>G (p.D191G) alteration is located in exon 4 (coding exon 4) of the BORCS5 gene. This alteration results from a A to G substitution at nucleotide position 572, causing the aspartic acid (D) at amino acid position 191 to be replaced by a glycine (G). 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

0.090

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0062

T;T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.64

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0096

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.93

D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

0.26

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.18

.;T;T

Polyphen

0.057, 0.0

.;B;B

Vest4

0.22

MVP

0.26

MPC

0.38

ClinPred

0.14

GERP RS

3.2

Varity_R

0.061

gMVP

0.59

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