chr19-16206365-C-G

Variant names:

• chr19-16206365-C-G
• NM_032493.4:c.224C>G

Variant summary

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

The NM_032493.4(AP1M1):​c.224C>G​(p.Ala75Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 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. A75V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AP1M1 NM_032493.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61

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

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
AP1M1	NM_032493.4	c.224C>G	p.Ala75Gly	missense_variant	Exon 3 of 12	ENST00000291439.8	NP_115882.1
AP1M1	NM_001130524.2	c.224C>G	p.Ala75Gly	missense_variant	Exon 3 of 13		NP_001123996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1M1	ENST00000291439.8	c.224C>G	p.Ala75Gly	missense_variant	Exon 3 of 12	1	NM_032493.4	ENSP00000291439.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727240

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	0.21
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.40	T;.;.;.;T;.;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.5	M;.;.;M;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.1	N;.;N;N;.;.;.;.
REVEL	Benign	0.24
Sift	Benign	0.047	D;.;D;D;.;.;.;.
Sift4G	Benign	0.080	T;T;T;T;D;T;D;T
Polyphen		0.84	P;.;B;.;.;.;.;.
Vest4		0.48
MutPred		0.36		Gain of ubiquitination at K72 (P = 0.0671);Gain of ubiquitination at K72 (P = 0.0671);Gain of ubiquitination at K72 (P = 0.0671);Gain of ubiquitination at K72 (P = 0.0671);.;.;.;.;
MVP		0.58
MPC		1.4
ClinPred		0.79	D
GERP RS		4.1
Varity_R		0.27
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: -24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-16317176;