NM_004722.4:c.19A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004722.4(AP4M1):c.19A>G(p.Ile7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,559,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I7L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AP4M1
NM_004722.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Publications

2 publications found

Variant links:

Genes affected

AP4M1 (HGNC:574): (adaptor related protein complex 4 subunit mu 1) This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system. [provided by RefSeq, Jul 2008]

AP4M1 links:

MCM7 (HGNC:6950): (minichromosome maintenance complex component 7) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MCM7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1894544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP4M1	NM_004722.4	MANE Select	c.19A>G	p.Ile7Val	missense	Exon 1 of 15	NP_004713.2
AP4M1	NM_001363671.2		c.19A>G	p.Ile7Val	missense	Exon 1 of 15	NP_001350600.1	C9JC87
AP4M1	NM_001438824.1		c.19A>G	p.Ile7Val	missense	Exon 2 of 16	NP_001425753.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP4M1	ENST00000359593.9	TSL:1 MANE Select	c.19A>G	p.Ile7Val	missense	Exon 1 of 15	ENSP00000352603.4	O00189
AP4M1	ENST00000421755.5	TSL:1	c.19A>G	p.Ile7Val	missense	Exon 1 of 16	ENSP00000412185.1	O00189
MCM7	ENST00000343023.10	TSL:1	c.-439T>C		5_prime_UTR	Exon 1 of 9	ENSP00000344006.6	P33993-2

Frequencies

GnomAD3 genomes

AF:

0.0000276

AC:

AN:

144974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000649

Gnomad SAS

AF:

0.000232

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

250902

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000120

AC:

AN:

1414808

Hom.:

Cov.:

AF XY:

0.00000995

AC XY:

AN XY:

703206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31510

American (AMR)

AF:

0.00

AC:

AN:

43564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24620

East Asian (EAS)

AF:

0.000430

AC:

AN:

37196

South Asian (SAS)

AF:

0.00

AC:

AN:

85800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1079208

Other (OTH)

AF:

0.00

AC:

AN:

57208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000276

AC:

AN:

145046

Hom.:

Cov.:

AF XY:

0.0000425

AC XY:

AN XY:

70596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39320

American (AMR)

AF:

0.00

AC:

AN:

14726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.000651

AC:

AN:

4608

South Asian (SAS)

AF:

0.000232

AC:

AN:

4302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66044

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000312

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.026

MetaRNN

Benign

0.19

MetaSVM

Uncertain

0.068

MutationAssessor

Benign

1.1

PhyloP100

3.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.26

REVEL

Uncertain

0.34

Sift

Benign

0.28

Sift4G

Benign

0.15

Polyphen

0.96

Vest4

0.50

MutPred

0.51

Gain of sheet (P = 0.0827)

MVP

0.75

MPC

0.13

ClinPred

0.16

GERP RS

5.7

PromoterAI

0.061

Neutral

(source)

Varity_R

0.20

gMVP

0.43

Mutation Taster

=214/86

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