19-10581287-C-A

Variant names:

• chr19-10581287-C-A
• rs751646389
• NM_005498.5:c.652G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005498.5(AP1M2):​c.652G>T​(p.Val218Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,461,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V218M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: AP1M2 NM_005498.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 publications found

Genes affected

AP1M2 (HGNC:558): (adaptor related protein complex 1 subunit mu 2) This gene encodes a subunit of the heterotetrameric adaptor-related protein comlex 1 (AP-1), which belongs to the adaptor complexes medium subunits family. This protein is capable of interacting with tyrosine-based sorting signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13868865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005498.5. 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
	AP1M2	NM_005498.5	MANE Select	c.652G>T	p.Val218Leu	missense	Exon 6 of 12	NP_005489.2
	AP1M2	NM_001300887.2		c.652G>T	p.Val218Leu	missense	Exon 6 of 12	NP_001287816.1	Q9Y6Q5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1M2	ENST00000250244.11	TSL:1 MANE Select	c.652G>T	p.Val218Leu	missense	Exon 6 of 12	ENSP00000250244.5	Q9Y6Q5-1
	AP1M2	ENST00000590923.5	TSL:1	c.652G>T	p.Val218Leu	missense	Exon 6 of 12	ENSP00000465685.1	Q9Y6Q5-2
	AP1M2	ENST00000918520.1		c.652G>T	p.Val218Leu	missense	Exon 6 of 12	ENSP00000588579.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000964 AC: 24 AN: 248940 AF XY: 0.0000666

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461286 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000649 AC: 29 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111586

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000549 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000661 AC: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.60	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.45	N
PhyloP100		4.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.84	T
Polyphen		0.0050	B
Vest4		0.59
MutPred		0.51		Gain of sheet (P = 0.1208)
MVP		0.15
MPC		0.16
ClinPred		0.11	T
GERP RS		4.4
Varity_R		0.17
gMVP		0.30
Mutation Taster		=40/60	disease causing

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: rs751646389; hg19: chr19-10691963;