12-12435649-C-T

Variant names:

• chr12-12435649-C-T
• rs76204637
• NM_058169.6:c.224C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_058169.6(BORCS5):​c.224C>T​(p.Ser75Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BORCS5 NM_058169.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80

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 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity BORC5_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38357204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS5	NM_058169.6	c.224C>T	p.Ser75Phe	missense_variant	Exon 3 of 4	ENST00000314565.9	NP_477517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS5	ENST00000314565.9	c.224C>T	p.Ser75Phe	missense_variant	Exon 3 of 4	1	NM_058169.6	ENSP00000321546.4
BORCS5	ENST00000298571.6	c.80C>T	p.Ser27Phe	missense_variant	Exon 2 of 3	1		ENSP00000298571.6
BORCS5	ENST00000542728.5	c.167C>T	p.Ser56Phe	missense_variant	Exon 3 of 4	3		ENSP00000443023.1
BORCS5	ENST00000543990.1	n.318C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250972 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135676

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461520 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727056

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.65	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.57	T;T;D
Sift4G	Uncertain	0.025	.;D;D
Polyphen		0.99, 0.0	.;D;B
Vest4		0.56
MutPred		0.54		.;Gain of catalytic residue at G72 (P = 5e-04);.;
MVP		0.72
MPC		1.0
ClinPred		0.89	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.56

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: rs76204637; hg19: chr12-12588583;