4-6716346-A-T

Variant names:

• chr4-6716346-A-T
• rs551244392
• NM_018366.3:c.137A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018366.3(BLOC1S4):​c.137A>T​(p.Asp46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D46N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BLOC1S4 NM_018366.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116778105).

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.137A>T	p.Asp46Val	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.137A>T	p.Asp46Val	missense	Exon 1 of 1	ENSP00000318128.3	Q9NUP1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.039
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.067	T
Polyphen		0.61	P
Vest4		0.21
MutPred		0.15		Loss of glycosylation at P43 (P = 0.115)
MVP		0.53
MPC		1.1
ClinPred		0.57	D
GERP RS		3.2
PromoterAI		-0.071	Neutral
Varity_R		0.24
gMVP		0.26
Mutation Taster		=95/5	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: rs551244392; hg19: chr4-6718073;