6-8062204-T-A

Variant names:

• chr6-8062204-T-A
• rs9405369
• NM_201280.3:c.195+330A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201280.3(BLOC1S5):​c.195+330A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,828 control chromosomes in the GnomAD database, including 5,849 homozygotes. 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: 𝑓 0.27 (5849 hom., cov: 32)
• Consequence: BLOC1S5 NM_201280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	NM_201280.3	MANE Select	c.195+330A>T		intron	N/A	NP_958437.1
	BLOC1S5	NM_001199322.1		c.-101+330A>T		intron	N/A	NP_001186251.1
	BLOC1S5	NM_001199323.1		c.195+330A>T		intron	N/A	NP_001186252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5	ENST00000397457.7	TSL:1 MANE Select	c.195+330A>T		intron	N/A	ENSP00000380598.2
	BLOC1S5	ENST00000244777.6	TSL:1	n.195+330A>T		intron	N/A	ENSP00000244777.2
	EEF1E1-BLOC1S5	ENST00000397456.2	TSL:3	n.*11+330A>T		intron	N/A	ENSP00000380597.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41108 AN: 151710 Hom.: 5840 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41153 AN: 151828 Hom.: 5849 Cov.: 32 AF XY: 0.270 AC XY: 20055 AN XY: 74220

African (AFR) AF: 0.335 AC: 13836 AN: 41338

American (AMR) AF: 0.274 AC: 4176 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 955 AN: 3466

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5162

South Asian (SAS) AF: 0.457 AC: 2198 AN: 4814

European-Finnish (FIN) AF: 0.172 AC: 1815 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16114 AN: 67920

Other (OTH) AF: 0.268 AC: 564 AN: 2104

Alfa AF: 0.141 Hom.: 244

Bravo AF: 0.279

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.67
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs9405369; hg19: chr6-8062437;