14-57274732-C-T

Variant names:

• chr14-57274732-C-T
• rs984970036
• NM_018229.4:c.563C>T

Variant summary

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

The NM_018229.4(AP5M1):​c.563C>T​(p.Ser188Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S188Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP5M1 NM_018229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

Genes affected

AP5M1 (HGNC:20192): (adaptor related protein complex 5 subunit mu 1) Involved in endosomal transport. Located in several cellular components, including cytosol; late endosome; and lysosome. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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 rank	MANE	Protein	UniProt
AP5M1	NM_018229.4	c.563C>T	p.Ser188Phe	missense_variant	Exon 2 of 8	ENST00000261558.8	NP_060699.3
AP5M1	XM_011536940.4	c.605C>T	p.Ser202Phe	missense_variant	Exon 3 of 9		XP_011535242.1
AP5M1	NR_026895.2	n.418+5344C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP5M1	ENST00000261558.8	c.563C>T	p.Ser188Phe	missense_variant	Exon 2 of 8	1	NM_018229.4	ENSP00000261558.3
AP5M1	ENST00000431972.6	c.605C>T	p.Ser202Phe	missense_variant	Exon 3 of 9	2		ENSP00000390531.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.090	T;T
Polyphen		0.88	P;.
Vest4		0.36
MutPred		0.30		Loss of disorder (P = 0.0071);.;
MVP		0.74
MPC		0.26
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.12
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs984970036; hg19: chr14-57741450; COSMIC: COSV55106940; COSMIC: COSV55106940;