dbSNP rs766753848: ENSG00000260170:c.-34C>T (chr15-45587509-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The ENST00000564080.1(ENSG00000260170):c.-34C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,425,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ENSG00000260170
ENST00000564080.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.257

Publications

0 publications found

Variant links:

Genes affected

ENSG00000260170 (HGNC:):

ENSG00000260170 links:

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

BLOC1S6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 15-45587509-C-T is Benign according to our data. Variant chr15-45587509-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2066467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000564080.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLOC1S6	NM_012388.4	MANE Select	c.66C>T	p.Ala22Ala	synonymous	Exon 1 of 5	NP_036520.1	Q9UL45-1
BLOC1S6	NR_132351.2		n.131C>T		non_coding_transcript_exon	Exon 1 of 5
BLOC1S6	NR_132352.2		n.131C>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENSG00000260170	ENST00000564080.1	TSL:3	c.-34C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000455047.1	H3BNX3
BLOC1S6	ENST00000220531.9	TSL:1 MANE Select	c.66C>T	p.Ala22Ala	synonymous	Exon 1 of 5	ENSP00000220531.4	Q9UL45-1
ENSG00000260170	ENST00000564080.1	TSL:3	c.-34C>T		5_prime_UTR	Exon 1 of 6	ENSP00000455047.1	H3BNX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000158

AC:

AN:

189286

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000375

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1425534

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

706030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32604

American (AMR)

AF:

0.00

AC:

AN:

40032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25510

East Asian (EAS)

AF:

0.00

AC:

AN:

37688

South Asian (SAS)

AF:

0.00

AC:

AN:

81814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

1093896

Other (OTH)

AF:

0.00

AC:

AN:

58926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000299

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hermansky-Pudlak syndrome 9 (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.5

(source)

DANN

Benign

0.94

PhyloP100

-0.26

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over