12-12361281-G-C

Variant names:

• chr12-12361281-G-C
• rs144877374
• NM_058169.6:c.134G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058169.6(BORCS5):​c.134G>C​(p.Arg45Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,136 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: BORCS5 NM_058169.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS5	NM_058169.6	c.134G>C	p.Arg45Pro	missense_variant	Exon 2 of 4	ENST00000314565.9	NP_477517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS5	ENST00000314565.9	c.134G>C	p.Arg45Pro	missense_variant	Exon 2 of 4	1	NM_058169.6	ENSP00000321546.4
BORCS5	ENST00000298571.6	c.58+3772G>C		intron_variant	Intron 1 of 2	1		ENSP00000298571.6
BORCS5	ENST00000542728.5	c.77G>C	p.Arg26Pro	missense_variant	Exon 2 of 4	3		ENSP00000443023.1
BORCS5	ENST00000543990.1	n.228G>C		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0018	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.45	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.31	T;T
Sift4G	Benign	0.36	.;T
Polyphen		1.0	.;D
Vest4		0.69
MutPred		0.36		.;Gain of catalytic residue at Q42 (P = 0.0016);
MVP		0.70
MPC		0.88
ClinPred		0.81	D
GERP RS		6.0
Varity_R		0.28
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs144877374; hg19: chr12-12514215;