dbSNP rs185906682: AP1M2:p.Arg104Gln (chr19-10581835-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005498.5(AP1M2):c.311G>A(p.Arg104Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000912 in 1,613,764 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

AP1M2
NM_005498.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Publications

8 publications found

Variant links:

Genes affected

AP1M2 (HGNC:558): (adaptor related protein complex 1 subunit mu 2) This gene encodes a subunit of the heterotetrameric adaptor-related protein comlex 1 (AP-1), which belongs to the adaptor complexes medium subunits family. This protein is capable of interacting with tyrosine-based sorting signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

AP1M2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04404813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005498.5. 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
	AP1M2	NM_005498.5	MANE Select	c.311G>A	p.Arg104Gln	missense	Exon 4 of 12	NP_005489.2
	AP1M2	NM_001300887.2		c.311G>A	p.Arg104Gln	missense	Exon 4 of 12	NP_001287816.1	Q9Y6Q5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP1M2	ENST00000250244.11	TSL:1 MANE Select	c.311G>A	p.Arg104Gln	missense	Exon 4 of 12	ENSP00000250244.5	Q9Y6Q5-1
AP1M2	ENST00000590923.5	TSL:1	c.311G>A	p.Arg104Gln	missense	Exon 4 of 12	ENSP00000465685.1	Q9Y6Q5-2
AP1M2	ENST00000918520.1		c.311G>A	p.Arg104Gln	missense	Exon 4 of 12	ENSP00000588579.1

Frequencies

GnomAD3 genomes

AF:

0.000724

AC:

110

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000797

AC:

200

AN:

251016

AF XY:

0.000781

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000932

AC:

1362

AN:

1461698

Hom.:

Cov.:

AF XY:

0.000902

AC XY:

656

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.00107

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00112

AC:

1245

AN:

1111948

Other (OTH)

AF:

0.000960

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000723

AC:

110

AN:

152066

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41462

American (AMR)

AF:

0.000786

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00113

AC:

AN:

67986

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000939

Hom.:

Bravo

AF:

0.000842

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000758

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00130

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.081

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.32

MutationAssessor

Pathogenic

3.0

PhyloP100

3.6

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.28

Sift

Benign

0.038

Sift4G

Uncertain

0.039

Polyphen

0.96

Vest4

0.33

MVP

0.84

MPC

0.33

ClinPred

0.079

GERP RS

3.9

Varity_R

0.41

gMVP

0.22

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over