chr2-223765159-CCATCAT-C

Variant names:

• chr2-223765159-CCATCAT-C
• rs10644138
• NM_001039569.2:c.429+48_429+53delATGATG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001039569.2(AP1S3):​c.429+48_429+53delATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000389 in 1,560,500 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00028 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S3	NM_001039569.2	c.429+48_429+53delATGATG		intron_variant	Intron 4 of 4	ENST00000396654.7	NP_001034658.1
AP1S3	XM_011510600.4	c.292-6415_292-6410delATGATG		intron_variant	Intron 3 of 3		XP_011508902.1
AP1S3	NR_110905.2	n.600+48_600+53delATGATG		intron_variant	Intron 5 of 5
AP1S3	NR_110906.2	n.452+48_452+53delATGATG		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000396654.7	c.429+48_429+53delATGATG		intron_variant	Intron 4 of 4	2	NM_001039569.2	ENSP00000379891.2
ENSG00000286239	ENST00000650969.1	n.*1393+48_*1393+53delATGATG		intron_variant	Intron 16 of 16			ENSP00000498456.1

Frequencies

GnomAD3 genomes AF: 0.000278 AC: 42 AN: 150904 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000956

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000414

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000396 AC: 80 AN: 201824 Hom.: 0 AF XY: 0.000391 AC XY: 43 AN XY: 109964

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000404

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000271

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000587

Gnomad OTH exome AF: 0.00142

GnomAD4 exome AF: 0.000401 AC: 565 AN: 1409476 Hom.: 4 AF XY: 0.000408 AC XY: 286 AN XY: 700752

Gnomad4 AFR exome AF: 0.000326

Gnomad4 AMR exome AF: 0.000464

Gnomad4 ASJ exome AF: 0.0000816

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000216

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 0.000335

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.000278 AC: 42 AN: 151024 Hom.: 1 Cov.: 0 AF XY: 0.000203 AC XY: 15 AN XY: 73738

Gnomad4 AFR AF: 0.0000973

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000956

Gnomad4 NFE AF: 0.000414

Gnomad4 OTH AF: 0.00143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10644138; hg19: chr2-224629876;