rs769031495

Variant names:

• chr19-10581590-C-G
• rs769031495
• NM_005498.5:c.443G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10581590-C-G
• chr19-10581590-C-T

Variant summary

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

The NM_005498.5(AP1M2):​c.443G>C​(p.Arg148Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,536 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. R148Q) 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: 4.73

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 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
AP1M2	NM_005498.5	c.443G>C	p.Arg148Pro	missense_variant	Exon 5 of 12	ENST00000250244.11	NP_005489.2
AP1M2	NM_001300887.2	c.443G>C	p.Arg148Pro	missense_variant	Exon 5 of 12		NP_001287816.1
AP1M2	XM_047438018.1	c.365G>C	p.Arg122Pro	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.443G>C	p.Arg148Pro	missense_variant	Exon 5 of 12	1	NM_005498.5	ENSP00000250244.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248926 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134994

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 6.84e-7 AC: 1 AN: 1461536 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	.;T;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.52	D;D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	.;N;.;.;.
REVEL	Benign	0.24
Sift	Benign	0.078	.;T;.;.;.
Sift4G	Benign	0.18	T;T;.;.;T
Polyphen		0.049	B;D;.;.;.
Vest4		0.68
MutPred		0.40		Loss of MoRF binding (P = 0.0439);Loss of MoRF binding (P = 0.0439);.;.;.;
MVP		0.86
MPC		0.59
ClinPred		0.72	D
GERP RS		4.9
Varity_R		0.31
gMVP		0.45

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

LitVar

Other links and lift over

dbSNP: rs769031495; hg19: chr19-10692266;