Variant 19-10584043-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005498.5(AP1M2):c.70G>A(p.Asp24Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000565 in 1,610,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

AP1M2
NM_005498.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

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:

AP1M2 (HGNC:):

AP1M2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1M2	NM_005498.5 linkuse as main transcript	c.70G>A	p.Asp24Asn	missense_variant	2/12	ENST00000250244.11	NP_005489.2	Q9Y6Q5-1
AP1M2	NM_001300887.2 linkuse as main transcript	c.70G>A	p.Asp24Asn	missense_variant	2/12		NP_001287816.1	Q9Y6Q5-2Q53GI5
AP1M2	XM_047438018.1 linkuse as main transcript	c.-9G>A		5_prime_UTR_variant	2/12		XP_047293974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1M2	ENST00000250244.11 linkuse as main transcript	c.70G>A	p.Asp24Asn	missense_variant	2/12	1	NM_005498.5	ENSP00000250244.5		Q9Y6Q5-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000452

AC:

AN:

243352

Hom.:

AF XY:

0.0000455

AC XY:

AN XY:

131896

show subpopulations

Gnomad AFR exome

AF:

0.0000688

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.0000723

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000562

AC:

AN:

1458610

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

725186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.70G>A (p.D24N) alteration is located in exon 2 (coding exon 2) of the AP1M2 gene. This alteration results from a G to A substitution at nucleotide position 70, causing the aspartic acid (D) at amino acid position 24 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T;.

Eigen

Benign

0.19

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.9

.;D;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.017

.;D;.

Sift4G

Uncertain

0.049

D;D;D

Polyphen

0.60

P;B;.

Vest4

0.88

MVP

0.92

MPC

0.19

ClinPred

0.35

GERP RS

4.4

Varity_R

0.44

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over