chr17-8189711-C-T

Variant summary

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

The NM_017622.3(BORCS6):​c.430G>A​(p.Asp144Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,599,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

BORCS6
NM_017622.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05
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=0.044679582).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BORCS6NM_017622.3 linkc.430G>A p.Asp144Asn 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.430G>A p.Asp144Asn missense_variant Exon 1 of 1 6 NM_017622.3 ENSP00000373669.4 Q96GS4
ENSG00000279152ENST00000622992.1 linkn.*23C>T downstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000570
AC:
13
AN:
228102
Hom.:
0
AF XY:
0.0000395
AC XY:
5
AN XY:
126554
show subpopulations
Gnomad AFR exome
AF:
0.0000726
Gnomad AMR exome
AF:
0.00
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:
0.000115
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000422
AC:
61
AN:
1446776
Hom.:
0
Cov.:
34
AF XY:
0.0000305
AC XY:
22
AN XY:
720330
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000522
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000689
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000336
AC:
4
EpiCase
AF:
0.0000545
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
Apr 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.430G>A (p.D144N) alteration is located in exon 1 (coding exon 1) of the BORCS6 gene. This alteration results from a G to A substitution at nucleotide position 430, causing the aspartic acid (D) at amino acid position 144 to be replaced by an asparagine (N). 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
0.086
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.026
Sift
Benign
0.081
T
Sift4G
Benign
0.25
T
Polyphen
0.0050
B
Vest4
0.16
MVP
0.014
ClinPred
0.055
T
GERP RS
3.3
Varity_R
0.069
gMVP
0.080

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: rs772452730; hg19: chr17-8093029; API