rs373514982

Variant names:

• chr10-100286649-G-A
• rs373514982
• NM_173809.5:c.11C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-100286649-G-A
• chr10-100286649-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173809.5(BLOC1S2):​c.11C>T​(p.Ala4Val) variant causes a missense change. The variant allele was found at a frequency of 0.000521 in 1,609,602 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: BLOC1S2 NM_173809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86
• Publications: 1 publications found

Genes affected

BLOC1S2 (HGNC:20984): (biogenesis of lysosomal organelles complex 1 subunit 2) This gene encodes a protein with multiple functions. The encoded protein has been found in association with the centrosome, shown to co-localize with gamma-tubulin, and also found to be one of the proteins in the BLOC-1 complex which functions in the formation of lysosome-related organelles. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08845043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173809.5. 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
	BLOC1S2	NM_173809.5	MANE Select	c.11C>T	p.Ala4Val	missense	Exon 1 of 5	NP_776170.2
	BLOC1S2	NM_001282439.2		c.11C>T	p.Ala4Val	missense	Exon 1 of 5	NP_001269368.1
	BLOC1S2	NM_001282437.2		c.-238C>T		5_prime_UTR	Exon 1 of 5	NP_001269366.1	Q6QNY1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S2	ENST00000370372.7	TSL:1 MANE Select	c.11C>T	p.Ala4Val	missense	Exon 1 of 5	ENSP00000359398.2	Q6QNY1-1
	BLOC1S2	ENST00000881083.1		c.11C>T	p.Ala4Val	missense	Exon 1 of 5	ENSP00000551142.1
	BLOC1S2	ENST00000881082.1		c.11C>T	p.Ala4Val	missense	Exon 1 of 5	ENSP00000551141.1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000221 AC: 52 AN: 235256 AF XY: 0.000270

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000442

Gnomad OTH exome AF: 0.000350

GnomAD4 exome AF: 0.000550 AC: 801 AN: 1457244 Hom.: 1 Cov.: 32 AF XY: 0.000509 AC XY: 369 AN XY: 724602

African (AFR) AF: 0.0000299 AC: 1 AN: 33392

American (AMR) AF: 0.0000898 AC: 4 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000685 AC: 760 AN: 1110250

Other (OTH) AF: 0.000600 AC: 36 AN: 60040

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74500

African (AFR) AF: 0.000120 AC: 5 AN: 41594

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000380 Hom.: 0

Bravo AF: 0.000272

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000374 AC: 3

ExAC AF: 0.000205 AC: 24

EpiCase AF: 0.000600

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.9
PrimateAI	Uncertain	0.66	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.42
MVP		0.59
MPC		0.49
ClinPred		0.10	T
GERP RS		4.0
PromoterAI		-0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.072
gMVP		0.36
Mutation Taster		=90/10	polymorphism

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: rs373514982; hg19: chr10-102046406; COSMIC: COSV58396876; COSMIC: COSV58396876;