19-16241592-C-T

Variant names:

• chr19-16241592-C-T
• rs2262138
• NM_032493.4:c.*7157C>T

Variant summary

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

The NM_032493.4(AP1M1):​c.*7157C>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 0.715 in 152,026 control chromosomes in the GnomAD database, including 39,068 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 0.71 (39067 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: AP1M1 NM_032493.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 10 publications found

Genes affected

AP1M1 (HGNC:13667): (adaptor related protein complex 1 subunit mu 1) The protein encoded by this gene is the medium chain of the trans-Golgi network clathrin-associated protein complex AP-1. The other components of this complex are beta-prime-adaptin, gamma-adaptin, and the small chain AP1S1. This complex is located at the Golgi vesicle and links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1M1	NM_032493.4	MANE Select	c.*7157C>T		3_prime_UTR	Exon 12 of 12	NP_115882.1	Q9BXS5-1
	AP1M1	NM_001130524.2		c.*7157C>T		3_prime_UTR	Exon 13 of 13	NP_001123996.1	Q9BXS5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1M1	ENST00000291439.8	TSL:1 MANE Select	c.*7157C>T		3_prime_UTR	Exon 12 of 12	ENSP00000291439.2	Q9BXS5-1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108566 AN: 151904 Hom.: 39036 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

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) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.715 AC: 108641 AN: 152022 Hom.: 39067 Cov.: 32 AF XY: 0.715 AC XY: 53144 AN XY: 74318

African (AFR) AF: 0.628 AC: 26012 AN: 41426

American (AMR) AF: 0.773 AC: 11797 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3207 AN: 5172

South Asian (SAS) AF: 0.721 AC: 3476 AN: 4824

European-Finnish (FIN) AF: 0.771 AC: 8150 AN: 10564

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51138 AN: 67990

Other (OTH) AF: 0.726 AC: 1532 AN: 2110

Alfa AF: 0.737 Hom.: 174675

Bravo AF: 0.709

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-1.4

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: rs2262138; hg19: chr19-16352403;