BLOC1S5 p.Thr57Ser

Variant names:

• chr6-8062560-T-A
• NM_201280.3:c.169A>T
• BLOC1S5 p.Thr57Ser

Your query was ambiguous. Multiple possible variants found:

• chr6-8062560-T-A
• chr6-8062559-G-C
• chr6-8062558-AGT-GGA
• chr6-8062558-AGT-TGA
• chr6-8062558-AGT-CGA
• chr6-8062558-AG-GC

Variant summary

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

The NM_201280.3(BLOC1S5):​c.169A>T​(p.Thr57Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. T57I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BLOC1S5 NM_201280.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72
• 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.169A>T	p.Thr57Ser	missense	Exon 2 of 5	NP_958437.1	Q8TDH9-1
	BLOC1S5	NM_001199323.1		c.169A>T	p.Thr57Ser	missense	Exon 2 of 4	NP_001186252.1	A0A0A0MTN6
	BLOC1S5	NM_001199322.1		c.-127A>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.169A>T	p.Thr57Ser	missense	Exon 2 of 5	ENSP00000380598.2	Q8TDH9-1
	BLOC1S5	ENST00000244777.6	TSL:1	n.169A>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000244777.2	G5E931
	EEF1E1-BLOC1S5	ENST00000397456.2	TSL:3	n.441A>T		non_coding_transcript_exon	Exon 4 of 7	ENSP00000380597.2	C9J1V9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.7
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.057	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.34
Mutation Taster		=280/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-8062793;