14-57294220-C-T

Position:

• chr14-57294220-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018229.4(AP5M1):​c.*5336C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 151,702 control chromosomes in the GnomAD database, including 50,149 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 0.76 (50149 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: AP5M1 NM_018229.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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]

AP5M1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5M1	NM_018229.4	c.*5336C>T		3_prime_UTR_variant	8/8	ENST00000261558.8	NP_060699.3
AP5M1	XM_011536940.4	c.*5336C>T		3_prime_UTR_variant	9/9		XP_011535242.1
AP5M1	NR_026895.2	n.6507C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP5M1	ENST00000261558.8	c.*5336C>T		3_prime_UTR_variant	8/8	1	NM_018229.4	ENSP00000261558.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115386 AN: 151584 Hom.: 50146 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.803

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.761 AC: 115409 AN: 151702 Hom.: 50149 Cov.: 31 AF XY: 0.769 AC XY: 57014 AN XY: 74164

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.971

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.803

Alfa AF: 0.887 Hom.: 29681

Bravo AF: 0.735

Asia WGS AF: 0.886 AC: 3081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.29

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: rs1889720; hg19: chr14-57760938;