rs373357882

Variant names:

• chr19-10581588-C-G
• NM_005498.5:c.445G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10581588-C-G
• chr19-10581588-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005498.5(AP1M2):​c.445G>C​(p.Val149Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. V149M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AP1M2 NM_005498.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12815681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1M2	NM_005498.5	c.445G>C	p.Val149Leu	missense_variant	Exon 5 of 12	ENST00000250244.11	NP_005489.2
AP1M2	NM_001300887.2	c.445G>C	p.Val149Leu	missense_variant	Exon 5 of 12		NP_001287816.1
AP1M2	XM_047438018.1	c.367G>C	p.Val123Leu	missense_variant	Exon 5 of 12		XP_047293974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1M2	ENST00000250244.11	c.445G>C	p.Val149Leu	missense_variant	Exon 5 of 12	1	NM_005498.5	ENSP00000250244.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461556 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727040

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.036	.;T;.;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.41	N;N;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.77	.;N;.;.;.
REVEL	Benign	0.20
Sift	Benign	0.51	.;T;.;.;.
Sift4G	Benign	0.77	T;T;.;.;T
Polyphen		0.0020	B;B;.;.;.
Vest4		0.57
MutPred		0.29		Loss of MoRF binding (P = 0.1343);Loss of MoRF binding (P = 0.1343);.;.;.;
MVP		0.66
MPC		0.15
ClinPred		0.35	T
GERP RS		4.9
Varity_R		0.15
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10692264;