rs773102903

Variant names:

• chr12-12361223-A-G
• rs773102903
• NM_058169.6:c.76A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_058169.6(BORCS5):​c.76A>G​(p.Lys26Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: BORCS5 NM_058169.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88
• Publications: 0 publications found

Genes affected

BORCS5 (HGNC:17950): (BLOC-1 related complex subunit 5) Involved in lysosome localization and organelle transport along microtubule. Located in cytoplasmic side of lysosomal membrane and plasma membrane. Is intrinsic component of membrane. Part of BORC complex. Colocalizes with plus-end kinesin complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.19828328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058169.6. 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
	BORCS5	NM_058169.6	MANE Select	c.76A>G	p.Lys26Glu	missense	Exon 2 of 4	NP_477517.1	Q969J3-1
	BORCS5	NM_001300742.3		c.19A>G	p.Lys7Glu	missense	Exon 2 of 4	NP_001287671.1	G3V1P3
	BORCS5	NM_001330356.2		c.58+3714A>G		intron	N/A	NP_001317285.1	Q969J3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS5	ENST00000314565.9	TSL:1 MANE Select	c.76A>G	p.Lys26Glu	missense	Exon 2 of 4	ENSP00000321546.4	Q969J3-1
	BORCS5	ENST00000298571.6	TSL:1	c.58+3714A>G		intron	N/A	ENSP00000298571.6	Q969J3-2
	BORCS5	ENST00000866053.1		c.139A>G	p.Lys47Glu	missense	Exon 3 of 5	ENSP00000536112.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000875 AC: 22 AN: 251480 AF XY: 0.0000883

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000141 AC: 206 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.000139 AC XY: 101 AN XY: 727200

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000160 AC: 178 AN: 1111954

Other (OTH) AF: 0.000199 AC: 12 AN: 60390

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74314

African (AFR) AF: 0.0000724 AC: 3 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000164

EpiControl AF: 0.000178

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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
PhyloP100		8.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Benign	0.20	T
Polyphen		0.39	B
Vest4		0.54
MutPred		0.29		Loss of ubiquitination at K26 (P = 0.0023)
MVP		0.50
MPC		0.51
ClinPred		0.087	T
GERP RS		6.0
Varity_R		0.36
gMVP		0.53
Mutation Taster		=60/40	polymorphism

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: rs773102903; hg19: chr12-12514157;