12-110436687-GA-GAAAA

Variant names:

• chr12-110436687-G-GAAA
• rs59861890
• NM_001278556.2:c.253-7_253-5dupTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001278556.2(ARPC3):​c.253-7_253-5dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 797,218 control chromosomes in the GnomAD database, including 2,254 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (485 hom., cov: 0)
  • Exomes 𝑓: 0.036 (1769 hom.)
• Consequence: ARPC3 NM_001278556.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

ARPC3 (HGNC:706): (actin related protein 2/3 complex subunit 3) This gene encodes one of seven subunits of the human Arp2/3 protein complex. The Arp2/3 protein complex has been conserved through evolution and is implicated in the control of actin polymerization in cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

ENSG00000258210 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC3	NM_001278556.2	c.253-7_253-5dupTTT		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000228825.12	NP_001265485.1
ARPC3	NM_001287222.2	c.253-7_253-5dupTTT		splice_region_variant, intron_variant	Intron 4 of 6		NP_001274151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC3	ENST00000228825.12	c.253-5_253-4insTTT		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_001278556.2	ENSP00000228825.7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 9010 AN: 85020 Hom.: 487 Cov.: 0

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00916

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.117

GnomAD3 exomes AF: 0.0323 AC: 4245 AN: 131236 Hom.: 173 AF XY: 0.0322 AC XY: 2315 AN XY: 71968

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.0200

Gnomad ASJ exome AF: 0.0984

Gnomad EAS exome AF: 0.00117

Gnomad SAS exome AF: 0.0354

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0344

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0361 AC: 25744 AN: 712172 Hom.: 1769 Cov.: 24 AF XY: 0.0371 AC XY: 13722 AN XY: 369778

Gnomad4 AFR exome AF: 0.0655

Gnomad4 AMR exome AF: 0.0217

Gnomad4 ASJ exome AF: 0.0982

Gnomad4 EAS exome AF: 0.00605

Gnomad4 SAS exome AF: 0.0394

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0442

GnomAD4 genome AF: 0.106 AC: 9005 AN: 85046 Hom.: 485 Cov.: 0 AF XY: 0.106 AC XY: 4189 AN XY: 39688

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.00920

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.116

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: rs59861890; hg19: chr12-110874492;