Genetic Variant NM_018366.3:c.329C>T (chr4-6716538-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018366.3(BLOC1S4):c.329C>T(p.Ser110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000386 in 1,556,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

BLOC1S4
NM_018366.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Publications

1 publications found

Variant links:

Genes affected

BLOC1S4 (HGNC:24206): (biogenesis of lysosomal organelles complex 1 subunit 4) This intronless gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and is a model for Hermansky-Pudlak syndrome. The encoded protein may play a role in intracellular vesicular trafficking. [provided by RefSeq, Jul 2008]

BLOC1S4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018366.3. 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
	BLOC1S4	NM_018366.3	MANE Select	c.329C>T	p.Ser110Leu	missense	Exon 1 of 1	NP_060836.1	Q9NUP1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S4	ENST00000320776.5	TSL:6 MANE Select	c.329C>T	p.Ser110Leu	missense	Exon 1 of 1	ENSP00000318128.3	Q9NUP1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000192

AC:

AN:

156034

AF XY:

0.0000351

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:

0.0000317

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1404090

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32290

American (AMR)

AF:

0.00

AC:

AN:

37424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25318

East Asian (EAS)

AF:

0.00

AC:

AN:

36640

South Asian (SAS)

AF:

0.0000371

AC:

AN:

80832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1087598

Other (OTH)

AF:

0.00

AC:

AN:

58536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000854

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.0084

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.37

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

2.9

PhyloP100

2.3

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.24

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.26

MutPred

0.40

Loss of disorder (P = 0.0127)

MVP

0.68

MPC

1.7

ClinPred

0.99

GERP RS

3.3

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.58

gMVP

0.72

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over