6-8059942-C-T

Variant names:

• chr6-8059942-C-T
• rs2743991
• NM_201280.3:c.195+2592G>A

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+2592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,100 control chromosomes in the GnomAD database, including 14,468 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 0.43 (14468 hom., cov: 33)
• Consequence: BLOC1S5 NM_201280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S5	NM_201280.3	c.195+2592G>A		intron_variant	Intron 2 of 4	ENST00000397457.7	NP_958437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S5	ENST00000397457.7	c.195+2592G>A		intron_variant	Intron 2 of 4	1	NM_201280.3	ENSP00000380598.2
EEF1E1-BLOC1S5	ENST00000397456.2	n.*11+2592G>A		intron_variant	Intron 4 of 6	3		ENSP00000380597.2
BLOC1S5-TXNDC5	ENST00000439343.2	n.183+2592G>A		intron_variant	Intron 2 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65541 AN: 151982 Hom.: 14455 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.431 AC: 65590 AN: 152100 Hom.: 14468 Cov.: 33 AF XY: 0.433 AC XY: 32188 AN XY: 74370

African (AFR) AF: 0.403 AC: 16712 AN: 41442

American (AMR) AF: 0.386 AC: 5898 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3466

East Asian (EAS) AF: 0.575 AC: 2973 AN: 5174

South Asian (SAS) AF: 0.308 AC: 1487 AN: 4828

European-Finnish (FIN) AF: 0.533 AC: 5644 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30253 AN: 67994

Other (OTH) AF: 0.385 AC: 814 AN: 2114

Alfa AF: 0.434 Hom.: 3705

Bravo AF: 0.422

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.79
PhyloP100		-0.96
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: rs2743991; hg19: chr6-8060175;