chr5-115913419-C-A

Variant names:

• chr5-115913419-C-A
• NM_001284.4:c.511C>A

Variant summary

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

The NM_001284.4(AP3S1):​c.511C>A​(p.Pro171Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 42)
• Consequence: AP3S1 NM_001284.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86
• Publications: 0 publications found

Genes affected

AP3S1 (HGNC:2013): (adaptor related protein complex 3 subunit sigma 1) This gene encodes a subunit of the AP3 adaptor complex. This complex functions in the formation of subcellular vesicles budded from the Golgi body. Several related pseudogenes of this gene have been found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

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_001284.4. 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
	AP3S1	NM_001284.4	MANE Select	c.511C>A	p.Pro171Thr	missense	Exon 6 of 6	NP_001275.1	Q92572
	AP3S1	NM_001364119.1		c.559C>A	p.Pro187Thr	missense	Exon 7 of 7	NP_001351048.1
	AP3S1	NM_001002924.3		c.445C>A	p.Pro149Thr	missense	Exon 7 of 7	NP_001002924.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S1	ENST00000316788.12	TSL:1 MANE Select	c.511C>A	p.Pro171Thr	missense	Exon 6 of 6	ENSP00000325369.7	Q92572
	AP3S1	ENST00000395548.6	TSL:1	n.588C>A		non_coding_transcript_exon	Exon 7 of 7
	AP3S1	ENST00000922028.1		c.661C>A	p.Pro221Thr	missense	Exon 6 of 6	ENSP00000592087.1

Frequencies

GnomAD3 genomes Cov.: 42

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 42

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Benign	0.043	D
Sift4G	Benign	0.13	T
Polyphen		0.97	D
Vest4		0.65
MutPred		0.51		Loss of helix (P = 0.0237)
MVP		0.68
MPC		1.5
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.23
gMVP		0.89
Mutation Taster		=46/54	disease causing

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

hg19: chr5-115249116;