rs561853521

Variant names:

• chr17-8189815-C-A
• rs561853521
• NM_017622.3:c.326G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8189815-C-A
• chr17-8189815-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017622.3(BORCS6):​c.326G>T​(p.Arg109Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: BORCS6 NM_017622.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• 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]

ENSG00000299228 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054220498).

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.326G>T	p.Arg109Leu	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.326G>T	p.Arg109Leu	missense	Exon 1 of 1	ENSP00000373669.4	Q96GS4
	ENSG00000299228	ENST00000761712.1		n.332C>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000279152	ENST00000622992.1	TSL:6	n.*127C>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431362 Hom.: 0 Cov.: 34 AF XY: 0.00000141 AC XY: 1 AN XY: 710998

African (AFR) AF: 0.00 AC: 0 AN: 32696

American (AMR) AF: 0.00 AC: 0 AN: 41108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 38182

South Asian (SAS) AF: 0.00 AC: 0 AN: 84240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100972

Other (OTH) AF: 0.0000169 AC: 1 AN: 59314

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.3
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.14
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.016
Sift	Benign	0.39	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.062
MutPred		0.19		Loss of solvent accessibility (P = 0.0238)
MVP		0.067
ClinPred		0.067	T
GERP RS		2.0
PromoterAI		-0.027	Neutral
Varity_R		0.11
gMVP		0.067

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: rs561853521; hg19: chr17-8093133;