rs76204637

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-12435649-C-A
• chr12-12435649-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_058169.6(BORCS5):​c.224C>A​(p.Ser75Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BORCS5 NM_058169.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80
• Publications: 1 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: Uncertain_significance. The variant received 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.224C>A	p.Ser75Tyr	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>A	p.Ser75Tyr	missense_variant	Exon 3 of 4	1	NM_058169.6	ENSP00000321546.4
BORCS5	ENST00000298571.6	c.80C>A	p.Ser27Tyr	missense_variant	Exon 2 of 3	1		ENSP00000298571.6
BORCS5	ENST00000542728.5	c.167C>A	p.Ser56Tyr	missense_variant	Exon 3 of 4	3		ENSP00000443023.1
BORCS5	ENST00000543990.1	n.318C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.020	T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.0	.;.;.
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.0	.;.;.
PhyloP100		5.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.87	T;T;D
Sift4G	Pathogenic	0.0	.;D;D
Vest4		0.76
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.54
Mutation Taster		=39/61	disease causing

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: rs76204637; hg19: chr12-12588583;