15-45587457-GG-CC

Variant names:

• chr15-45587457-GG-CC
• NM_012388.4:c.14_15delGGinsCC
• BLOC1S6 p.Gly5Ala

Variant summary

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

The NM_012388.4(BLOC1S6):​c.14_15delGGinsCC​(p.Gly5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. G5V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BLOC1S6 NM_012388.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

Genes affected

BLOC1S6 (HGNC:8549): (biogenesis of lysosomal organelles complex 1 subunit 6) The protein encoded by this gene may play a role in intracellular vesicle trafficking. It interacts with Syntaxin 13 which mediates intracellular membrane fusion. Mutations in this gene cause symptoms associated with Hermansky-Pudlak syndrome-9. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the X chromosome. [provided by RefSeq, Aug 2015]

BLOC1S6 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000260170 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012388.4. 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
	BLOC1S6	NM_012388.4	MANE Select	c.14_15delGGinsCC	p.Gly5Ala	missense	N/A	NP_036520.1	Q9UL45-1
	BLOC1S6	NR_132351.2		n.79_80delGGinsCC		non_coding_transcript_exon	Exon 1 of 5
	BLOC1S6	NR_132352.2		n.79_80delGGinsCC		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S6	ENST00000220531.9	TSL:1 MANE Select	c.14_15delGGinsCC	p.Gly5Ala	missense	N/A	ENSP00000220531.4	Q9UL45-1
	ENSG00000260170	ENST00000564080.1	TSL:3	c.-86_-85delGGinsCC		5_prime_UTR	Exon 1 of 6	ENSP00000455047.1	H3BNX3
	BLOC1S6	ENST00000565216.5	TSL:3	c.14_15delGGinsCC	p.Gly5Ala	missense	N/A	ENSP00000456067.1	H3BR42

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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: chr15-45879655;