chr8-42154785-T-C

Variant names:

• chr8-42154785-T-C
• NM_006803.4:c.98T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006803.4(AP3M2):​c.98T>C​(p.Phe33Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP3M2 NM_006803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

AP3M2 (HGNC:570): (adaptor related protein complex 3 subunit mu 2) This gene encodes a subunit of the heterotetrameric adaptor-related protein comlex 3 (AP-3), which belongs to the adaptor complexes medium subunits family. The AP-3 complex plays a role in protein trafficking to lysosomes and specialized organelles. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006803.4. 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
	AP3M2	NM_006803.4	MANE Select	c.98T>C	p.Phe33Ser	missense	Exon 2 of 9	NP_006794.1	A0A384NYL6
	AP3M2	NM_001134296.2		c.98T>C	p.Phe33Ser	missense	Exon 3 of 10	NP_001127768.1	A0A384NYL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3M2	ENST00000396926.8	TSL:1 MANE Select	c.98T>C	p.Phe33Ser	missense	Exon 2 of 9	ENSP00000380132.3	P53677-1
	AP3M2	ENST00000518421.5	TSL:1	c.98T>C	p.Phe33Ser	missense	Exon 3 of 10	ENSP00000428787.1	P53677-1
	AP3M2	ENST00000517865.5	TSL:1	n.98T>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000430200.1	E5RGF3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.93
MutPred		0.60		Gain of disorder (P = 0.003)
MVP		0.96
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
PromoterAI		0.0067	Neutral
Varity_R		0.82
gMVP		0.69
Mutation Taster		=27/73	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: chr8-42012303;