NM_017622.3:c.466G>T

Variant names:

• chr17-8189675-C-A
• NM_017622.3:c.466G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/19 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)
• Consequence: BORCS6 NM_017622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.641
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19556364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017622.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS6	NM_017622.3	MANE Select	c.466G>T	p.Gly156Cys	missense	Exon 1 of 1	NP_060092.2	Q96GS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS6	ENST00000389017.6	TSL:6 MANE Select	c.466G>T	p.Gly156Cys	missense	Exon 1 of 1	ENSP00000373669.4	Q96GS4
	ENSG00000279152	ENST00000622992.1	TSL:6	n.743C>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000299228	ENST00000761712.1		n.192C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.64
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

Other links and lift over

hg19: chr17-8092993;