rs370465146

Variant names:

• chr6-8062556-C-A
• rs370465146
• NM_201280.3:c.173G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-8062556-C-A
• chr6-8062556-C-T

Variant summary

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

The NM_201280.3(BLOC1S5):​c.173G>T​(p.Arg58Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,290 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R58H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BLOC1S5 NM_201280.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• Publications: 0 publications found

Genes affected

BLOC1S5 (HGNC:18561): (biogenesis of lysosomal organelles complex 1 subunit 5) This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky-Pudlak Syndrome is mutated in the murine version of this gene. Alternative splicing results in multiple transcript variants. Read-through transcription exists between this gene and the upstream EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) gene, as well as with the downstream TXNDC5 (thioredoxin domain containing 5) gene. [provided by RefSeq, Dec 2010]

EEF1E1-BLOC1S5 (HGNC:49187): (EEF1E1-BLOC1S5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) and MUTED (muted homolog) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201280.3. 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
	BLOC1S5	NM_201280.3	MANE Select	c.173G>T	p.Arg58Leu	missense	Exon 2 of 5	NP_958437.1	Q8TDH9-1
	BLOC1S5	NM_001199323.1		c.173G>T	p.Arg58Leu	missense	Exon 2 of 4	NP_001186252.1	A0A0A0MTN6
	BLOC1S5	NM_001199322.1		c.-123G>T		5_prime_UTR	Exon 2 of 6	NP_001186251.1	Q8TDH9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	ENST00000397457.7	TSL:1 MANE Select	c.173G>T	p.Arg58Leu	missense	Exon 2 of 5	ENSP00000380598.2	Q8TDH9-1
	BLOC1S5	ENST00000244777.6	TSL:1	n.173G>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000244777.2	G5E931
	EEF1E1-BLOC1S5	ENST00000397456.2	TSL:3	n.445G>T		non_coding_transcript_exon	Exon 4 of 7	ENSP00000380597.2	C9J1V9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441290 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 717682

African (AFR) AF: 0.00 AC: 0 AN: 32728

American (AMR) AF: 0.00 AC: 0 AN: 42284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25744

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.00 AC: 0 AN: 83736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098930

Other (OTH) AF: 0.00 AC: 0 AN: 59626

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.7
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.064	B
Vest4		0.84
MutPred		0.50		Loss of disorder (P = 0.0607)
MVP		0.56
MPC		0.41
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.52
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs370465146; hg19: chr6-8062789;