NM_018229.4:c.74+1363A>G

Variant names:

• chr14-57270751-A-G
• rs7141198
• NM_018229.4:c.74+1363A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018229.4(AP5M1):​c.74+1363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,176 control chromosomes in the GnomAD database, including 12,188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (12188 hom., cov: 32)
• Consequence: AP5M1 NM_018229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5M1	NM_018229.4	MANE Select	c.74+1363A>G		intron	N/A	NP_060699.3
	AP5M1	NR_026895.2		n.418+1363A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5M1	ENST00000261558.8	TSL:1 MANE Select	c.74+1363A>G		intron	N/A	ENSP00000261558.3
	AP5M1	ENST00000431972.6	TSL:2	c.74+1363A>G		intron	N/A	ENSP00000390531.2
	AP5M1	ENST00000554931.1	TSL:1	n.465+1363A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38487 AN: 152058 Hom.: 12142 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38588 AN: 152176 Hom.: 12188 Cov.: 32 AF XY: 0.245 AC XY: 18225 AN XY: 74412

African (AFR) AF: 0.751 AC: 31125 AN: 41468

American (AMR) AF: 0.120 AC: 1829 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.0577 AC: 299 AN: 5180

South Asian (SAS) AF: 0.0853 AC: 412 AN: 4828

European-Finnish (FIN) AF: 0.0294 AC: 312 AN: 10620

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3753 AN: 68002

Other (OTH) AF: 0.208 AC: 439 AN: 2114

Alfa AF: 0.172 Hom.: 901

Bravo AF: 0.282

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7141198; hg19: chr14-57737469;