14-57294220-C-T

Variant names:

• chr14-57294220-C-T
• rs1889720
• NM_018229.4:c.*5336C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ENSG00000286355 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AP5M1	NM_018229.4	c.*5336C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000261558.8	NP_060699.3
AP5M1	NR_026895.2	n.6507C>T		non_coding_transcript_exon_variant	Exon 7 of 7
AP5M1	XM_011536940.4	c.*5336C>T		3_prime_UTR_variant	Exon 9 of 9		XP_011535242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP5M1	ENST00000261558.8	c.*5336C>T		3_prime_UTR_variant	Exon 8 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.299 AC: 12380 AN: 41406

American (AMR) AF: 0.888 AC: 13495 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3146 AN: 3462

East Asian (EAS) AF: 0.942 AC: 4858 AN: 5156

South Asian (SAS) AF: 0.915 AC: 4423 AN: 4832

European-Finnish (FIN) AF: 0.971 AC: 10304 AN: 10616

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 63999 AN: 67724

Other (OTH) AF: 0.803 AC: 1695 AN: 2110

Alfa AF: 0.867 Hom.: 111494

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
PhyloP100		0.13

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

Other links and lift over

dbSNP: rs1889720; hg19: chr14-57760938;