chr10-74129948-T-C

Variant names:

• chr10-74129948-T-C
• NM_012095.6:c.628A>G

Variant summary

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

The NM_012095.6(AP3M1):​c.628A>G​(p.Ile210Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP3M1 NM_012095.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

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]

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=0.11752921).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3M1	NM_012095.6	MANE Select	c.628A>G	p.Ile210Val	missense	Exon 5 of 9	NP_036227.1	Q9Y2T2
	AP3M1	NM_001320263.2		c.628A>G	p.Ile210Val	missense	Exon 7 of 11	NP_001307192.1	Q9Y2T2
	AP3M1	NM_001320264.2		c.628A>G	p.Ile210Val	missense	Exon 5 of 9	NP_001307193.1	Q9Y2T2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3M1	ENST00000355264.9	TSL:1 MANE Select	c.628A>G	p.Ile210Val	missense	Exon 5 of 9	ENSP00000347408.4	Q9Y2T2
	AP3M1	ENST00000372745.1	TSL:1	c.628A>G	p.Ile210Val	missense	Exon 6 of 10	ENSP00000361831.1	Q9Y2T2
	AP3M1	ENST00000867215.1		c.628A>G	p.Ile210Val	missense	Exon 6 of 10	ENSP00000537274.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	Benign	0.067
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.53
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N
PhyloP100		4.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	0.92	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.47		Gain of methylation at K211 (P = 0.0659)
MVP		0.21
MPC		0.30
ClinPred		0.64	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.13
Mutation Taster		=89/11	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

hg19: chr10-75889706;