NM_201280.3:c.112+463T>C

Variant names:

• chr6-8063802-A-G
• rs2743989
• NM_201280.3:c.112+463T>C

Variant summary

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

The NM_201280.3(BLOC1S5):​c.112+463T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,086 control chromosomes in the GnomAD database, including 36,523 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 0.69 (36523 hom., cov: 32)
• Consequence: BLOC1S5 NM_201280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 3 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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.112+463T>C		intron	N/A	NP_958437.1
	BLOC1S5	NM_001199322.1		c.-184+463T>C		intron	N/A	NP_001186251.1
	BLOC1S5	NM_001199323.1		c.112+463T>C		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.112+463T>C		intron	N/A	ENSP00000380598.2
	BLOC1S5	ENST00000244777.6	TSL:1	n.112+463T>C		intron	N/A	ENSP00000244777.2
	EEF1E1-BLOC1S5	ENST00000397456.2	TSL:3	n.385-1186T>C		intron	N/A	ENSP00000380597.2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104587 AN: 151968 Hom.: 36498 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.688 AC: 104674 AN: 152086 Hom.: 36523 Cov.: 32 AF XY: 0.693 AC XY: 51495 AN XY: 74326

African (AFR) AF: 0.682 AC: 28312 AN: 41486

American (AMR) AF: 0.713 AC: 10905 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2034 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5156 AN: 5176

South Asian (SAS) AF: 0.743 AC: 3587 AN: 4826

European-Finnish (FIN) AF: 0.720 AC: 7605 AN: 10568

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45206 AN: 67956

Other (OTH) AF: 0.638 AC: 1350 AN: 2116

Alfa AF: 0.674 Hom.: 11871

Bravo AF: 0.687

Asia WGS AF: 0.852 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.53
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: rs2743989; hg19: chr6-8064035;