Variant 19-10577253-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005498.5(AP1M2):c.992G>C(p.Ser331Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AP1M2
NM_005498.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.781

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096227735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1M2	NM_005498.5 link	c.992G>C	p.Ser331Thr	missense_variant	9/12	ENST00000250244.11	NP_005489.2	Q9Y6Q5-1
AP1M2	NM_001300887.2 link	c.998G>C	p.Ser333Thr	missense_variant	9/12		NP_001287816.1	Q9Y6Q5-2Q53GI5
AP1M2	XM_047438018.1 link	c.920G>C	p.Ser307Thr	missense_variant	9/12		XP_047293974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1M2	ENST00000250244.11 link	c.992G>C	p.Ser331Thr	missense_variant	9/12	1	NM_005498.5	ENSP00000250244.5		Q9Y6Q5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248114

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134644

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

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

Nov 18, 2022

The c.992G>C (p.S331T) alteration is located in exon 9 (coding exon 9) of the AP1M2 gene. This alteration results from a G to C substitution at nucleotide position 992, causing the serine (S) at amino acid position 331 to be replaced by a threonine (T). 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

0.060

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.049

.;.;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.096

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

.;.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.88

.;.;N;.

REVEL

Benign

0.092

Sift

Benign

0.51

.;.;T;.

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0010

.;B;B;.

Vest4

0.20, 0.20

MutPred

0.48

.;.;Loss of disorder (P = 0.0671);.;

MVP

0.11

MPC

0.15

ClinPred

0.067

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.084

gMVP

0.12

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

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