12-12465645-G-T

Variant names:

• chr12-12465645-G-T
• NM_058169.6:c.460G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058169.6(BORCS5):​c.460G>T​(p.Ala154Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BORCS5 NM_058169.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16218534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS5	NM_058169.6	c.460G>T	p.Ala154Ser	missense_variant	Exon 4 of 4	ENST00000314565.9	NP_477517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS5	ENST00000314565.9	c.460G>T	p.Ala154Ser	missense_variant	Exon 4 of 4	1	NM_058169.6	ENSP00000321546.4
BORCS5	ENST00000298571.6	c.316G>T	p.Ala106Ser	missense_variant	Exon 3 of 3	1		ENSP00000298571.6
BORCS5	ENST00000542728.5	c.403G>T	p.Ala135Ser	missense_variant	Exon 4 of 4	3		ENSP00000443023.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461872 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.84
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-0.090
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.44	N;N;N
REVEL	Benign	0.087
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.81	.;T;T
Polyphen		0.018, 0.0010	.;B;B
Vest4		0.17
MutPred		0.48		.;Gain of catalytic residue at R158 (P = 0.0068);.;
MVP		0.38
MPC		0.28
ClinPred		0.81	D
GERP RS		4.7
Varity_R		0.084
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-12618579;