Genetic Variant NM_017622.3:c.326G>C (chr17-8189815-C-G) – ACMG Classification: Likely_benign (-2 pts)

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: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

BORCS6
NM_017622.3 missense

Scores

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]

BORCS6 links:

ENSG00000279152 (HGNC:):

ENSG00000279152 links:

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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
BORCS6	NM_017622.3 link	c.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
BORCS6	ENST00000389017.6 link	c.326G>C	p.Arg109Pro	missense_variant	Exon 1 of 1	6	NM_017622.3	ENSP00000373669.4		Q96GS4
ENSG00000279152	ENST00000622992.1 link	n.*127C>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

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:

AN:

186324

Hom.:

AF XY:

0.000115

AC XY:

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:

AN:

1431360

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

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:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

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:

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

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.019

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

M_CAP

Benign

0.013

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.050

REVEL

Benign

0.030

Sift

Benign

0.15

Sift4G

Benign

0.20

Polyphen

0.91

Vest4

0.078

MutPred

0.21

Loss of stability (P = 0.0259);

MVP

0.088

ClinPred

0.036

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.

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