Genetic Variant AP3M1:p.Val79Ile (chr10-74138145-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_012095.6(AP3M1):c.235G>A(p.Val79Ile) 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 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. V79L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

AP3M1
NM_012095.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

0 publications found

Variant links:

Genes affected

AP3M1 (HGNC:569): (adaptor related protein complex 3 subunit mu 1) The protein encoded by this gene is the medium subunit of AP-3, which is an adaptor-related protein complex associated with the Golgi region as well as more peripheral intracellular structures. AP-3 facilitates the budding of vesicles from the Golgi membrane, and it may directly function in protein sorting to the endosomal/lysosomal system. AP-3 is a heterotetrameric protein complex composed of two large subunits (delta and beta3), a medium subunit (mu3), and a small subunit (sigma 3). Mutations in one of the large subunits of AP-3 have been associated with the Hermansky-Pudlak syndrome, a genetic disorder characterized by defective lysosome-related organelles. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2016]

AP3M1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27404654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012095.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3M1	NM_012095.6	MANE Select	c.235G>A	p.Val79Ile	missense	Exon 2 of 9	NP_036227.1	Q9Y2T2
AP3M1	NM_001320263.2		c.235G>A	p.Val79Ile	missense	Exon 4 of 11	NP_001307192.1	Q9Y2T2
AP3M1	NM_001320264.2		c.235G>A	p.Val79Ile	missense	Exon 2 of 9	NP_001307193.1	Q9Y2T2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3M1	ENST00000355264.9	TSL:1 MANE Select	c.235G>A	p.Val79Ile	missense	Exon 2 of 9	ENSP00000347408.4	Q9Y2T2
AP3M1	ENST00000372745.1	TSL:1	c.235G>A	p.Val79Ile	missense	Exon 3 of 10	ENSP00000361831.1	Q9Y2T2
AP3M1	ENST00000867215.1		c.235G>A	p.Val79Ile	missense	Exon 3 of 10	ENSP00000537274.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.025

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.0

PhyloP100

7.6

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.74

REVEL

Uncertain

0.35

Sift

Benign

0.16

Sift4G

Benign

0.17

Polyphen

0.29

Vest4

0.35

MutPred

0.58

Gain of catalytic residue at L77 (P = 0.3619)

MVP

0.48

MPC

0.49

ClinPred

0.85

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.51

Mutation Taster

=68/32

polymorphism

(source)

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

Publications

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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