rs762843731

Variant names:

• chr7-100106446-G-A
• NM_004722.4:c.1069G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100106446-G-A
• chr7-100106446-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004722.4(AP4M1):​c.1069G>A​(p.Ala357Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP4M1 NM_004722.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649

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]

ACMG classification

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=0.100283384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP4M1	NM_004722.4	c.1069G>A	p.Ala357Thr	missense_variant	Exon 14 of 15	ENST00000359593.9	NP_004713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP4M1	ENST00000359593.9	c.1069G>A	p.Ala357Thr	missense_variant	Exon 14 of 15	1	NM_004722.4	ENSP00000352603.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.65
DEOGEN2	Benign	0.072	T;T;.;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.73	T;T;.;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	.;.;N;N;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.69	N;N;N;N;N;N
REVEL	Benign	0.013
Sift	Benign	0.52	T;T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T;T
Polyphen		0.0090, 0.0010	.;B;B;B;.;.
Vest4		0.14, 0.14, 0.15, 0.14
MutPred		0.30		.;Gain of phosphorylation at A364 (P = 0.0598);.;.;.;.;
MVP		0.40
MPC		0.10
ClinPred		0.041	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.079
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99704069;