rs574333116

Variant names:

• chr15-45603169-G-A
• NM_012388.4:c.294G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-45603169-G-A
• chr15-45603169-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012388.4(BLOC1S6):​c.294G>A​(p.Met98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in Lovd.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BLOC1S6 NM_012388.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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]

ENSG00000260170 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17467716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S6	NM_012388.4	c.294G>A	p.Met98Ile	missense_variant	Exon 3 of 5	ENST00000220531.9	NP_036520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S6	ENST00000220531.9	c.294G>A	p.Met98Ile	missense_variant	Exon 3 of 5	1	NM_012388.4	ENSP00000220531.4
ENSG00000260170	ENST00000564080.1	c.-18+15644G>A		intron_variant	Intron 1 of 5	3		ENSP00000455047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445924 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 720294

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T;T;T;.;T;.;T;T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.0013
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.79	T;.;.;T;T;D;.;T;D;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.19	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.40	T;T;T;T;T;.;T;T;T;D
Sift4G	Benign	0.60	T;T;T;T;T;.;T;T;T;.
Polyphen		0.0010	B;.;.;.;.;.;.;.;.;.
Vest4		0.17
MutPred		0.23		Loss of catalytic residue at M98 (P = 0.0623);.;.;.;.;.;.;.;.;.;
MVP		0.15
MPC		0.45
ClinPred		0.76	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45895367;