chr17-8189377-G-T

Variant names:

• chr17-8189377-G-T
• rs745655945
• NM_017622.3:c.764C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017622.3(BORCS6):​c.764C>A​(p.Pro255Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BORCS6 NM_017622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.30
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3381964).

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.764C>A	p.Pro255Gln	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.764C>A	p.Pro255Gln	missense	Exon 1 of 1	ENSP00000373669.4	Q96GS4
	ENSG00000279152	ENST00000622992.1	TSL:6	n.445G>T		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000299228	ENST00000761712.1		n.-107G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449428 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 720194

African (AFR) AF: 0.00 AC: 0 AN: 33048

American (AMR) AF: 0.00 AC: 0 AN: 42690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39008

South Asian (SAS) AF: 0.00 AC: 0 AN: 84982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106176

Other (OTH) AF: 0.00 AC: 0 AN: 59858

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	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.67	T
PhyloP100		8.3
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.34
Sift	Benign	0.14	T
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.49		Loss of catalytic residue at P255 (P = 0.0193)
MVP		0.11
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.78

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

dbSNP: rs745655945; hg19: chr17-8092695;