17-8189675-C-A

Variant names:

• chr17-8189675-C-A
• NM_017622.3:c.466G>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.466G>T​(p.Gly156Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BORCS6 NM_017622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.641

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=0.19556364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS6	NM_017622.3	c.466G>T	p.Gly156Cys	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.466G>T	p.Gly156Cys	missense_variant	Exon 1 of 1	6	NM_017622.3	ENSP00000373669.4
ENSG00000279152	ENST00000622992.1	n.743C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.466G>T (p.G156C) alteration is located in exon 1 (coding exon 1) of the BORCS6 gene. This alteration results from a G to T substitution at nucleotide position 466, causing the glycine (G) at amino acid position 156 to be replaced by a cysteine (C). 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	0.19
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.94	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.23		Loss of methylation at R157 (P = 0.0452);
MVP		0.092
ClinPred		0.78	D
GERP RS		-1.9
Varity_R		0.25
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8092993;