14-57274732-C-G

Variant names:

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

Variant summary

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

The NM_018229.4(AP5M1):​c.563C>G​(p.Ser188Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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>G	p.Ser188Cys	missense_variant	Exon 2 of 8	ENST00000261558.8	NP_060699.3
AP5M1	XM_011536940.4	c.605C>G	p.Ser202Cys	missense_variant	Exon 3 of 9		XP_011535242.1
AP5M1	NR_026895.2	n.418+5344C>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP5M1	ENST00000261558.8	c.563C>G	p.Ser188Cys	missense_variant	Exon 2 of 8	1	NM_018229.4	ENSP00000261558.3
AP5M1	ENST00000431972.6	c.605C>G	p.Ser202Cys	missense_variant	Exon 3 of 9	2		ENSP00000390531.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.072	T;T
Polyphen		0.99	D;.
Vest4		0.35
MutPred		0.33		Loss of disorder (P = 0.0081);.;
MVP		0.78
MPC		0.38
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.10
gMVP		0.35

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

Other links and lift over

dbSNP: rs984970036; hg19: chr14-57741450;