17-8189668-G-A

Variant names:

• chr17-8189668-G-A
• NM_017622.3:c.473C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017622.3(BORCS6):​c.473C>T​(p.Ser158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,445,984 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: BORCS6 NM_017622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

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]

ENSG00000279152 (HGNC:):

ACMG classification

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=0.100070745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS6	NM_017622.3	c.473C>T	p.Ser158Leu	missense_variant	Exon 1 of 1	ENST00000389017.6	NP_060092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS6	ENST00000389017.6	c.473C>T	p.Ser158Leu	missense_variant	Exon 1 of 1	6	NM_017622.3	ENSP00000373669.4
ENSG00000279152	ENST00000622992.1	n.736G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000830 AC: 12 AN: 1445984 Hom.: 0 Cov.: 34 AF XY: 0.00000556 AC XY: 4 AN XY: 719884

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: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473C>T (p.S158L) alteration is located in exon 1 (coding exon 1) of the BORCS6 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the serine (S) at amino acid position 158 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.042
Sift	Uncertain	0.013	D
Sift4G	Benign	0.12	T
Polyphen		0.46	P
Vest4		0.041
MutPred		0.22		Loss of phosphorylation at S158 (P = 0.0095);
MVP		0.13
ClinPred		0.50	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8092986;