rs998508971

Variant names:

• chr2-223775925-C-G
• NM_001039569.2:c.267G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-223775925-C-G
• chr2-223775925-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001039569.2(AP1S3):​c.267G>C​(p.Glu89Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP1S3 NM_001039569.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

Genes affected

AP1S3 (HGNC:18971): (adaptor related protein complex 1 subunit sigma 3) This gene encodes a member of the adaptor-related protein complex 1, sigma subunit genes. The encoded protein is a component of adaptor protein complex 1 (AP-1), one of the AP complexes involved in claathrin-mediated vesicular transport from the Golgi or endosomes. Disruption of the pathway for display of HIV-1 antigens, which prevents recognition of the virus by cytotoxic T cells, has been shown to involve the AP-1 complex (PMID: 15569716). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000286239 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S3	NM_001039569.2	c.267G>C	p.Glu89Asp	missense_variant	Exon 3 of 5	ENST00000396654.7	NP_001034658.1
AP1S3	XM_011510600.4	c.267G>C	p.Glu89Asp	missense_variant	Exon 3 of 4		XP_011508902.1
AP1S3	NR_110905.2	n.399G>C		non_coding_transcript_exon_variant	Exon 3 of 6
AP1S3	NR_110906.2	n.314+1766G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000396654.7	c.267G>C	p.Glu89Asp	missense_variant	Exon 3 of 5	2	NM_001039569.2	ENSP00000379891.2
ENSG00000286239	ENST00000650969.1	n.*1231G>C		non_coding_transcript_exon_variant	Exon 15 of 17			ENSP00000498456.1
ENSG00000286239	ENST00000650969.1	n.*1231G>C		3_prime_UTR_variant	Exon 15 of 17			ENSP00000498456.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;.;T;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	4.2	H;H;H;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.94, 0.99	.;P;D;.
Vest4		0.93
MutPred		0.78		Loss of ubiquitination at K93 (P = 0.1741);Loss of ubiquitination at K93 (P = 0.1741);Loss of ubiquitination at K93 (P = 0.1741);Loss of ubiquitination at K93 (P = 0.1741);
MVP		0.83
MPC		0.36
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.81
gMVP		0.55

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: chr2-224640642;