12-110436687-GA-GAAA

Variant names:

• chr12-110436687-G-GAA
• rs59861890
• NM_001278556.2:c.253-6_253-5dupTT

Variant summary

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

The NM_001278556.2(ARPC3):​c.253-6_253-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 799,386 control chromosomes in the GnomAD database, including 979 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.098 (323 hom., cov: 0)
  • Exomes 𝑓: 0.016 (656 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 (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC3	NM_001278556.2	c.253-6_253-5dupTT		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000228825.12	NP_001265485.1
ARPC3	NM_001287222.2	c.253-6_253-5dupTT		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_253-4insTT		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_001278556.2	ENSP00000228825.7

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 8243 AN: 84478 Hom.: 323 Cov.: 0

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.0126 AC: 1656 AN: 131236 Hom.: 103 AF XY: 0.0125 AC XY: 903 AN XY: 71968

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.00950

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.0104

Gnomad SAS exome AF: 0.0170

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.0128

GnomAD4 exome AF: 0.0163 AC: 11654 AN: 714882 Hom.: 656 Cov.: 24 AF XY: 0.0166 AC XY: 6165 AN XY: 371198

Gnomad4 AFR exome AF: 0.0382

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.0209

Gnomad4 FIN exome AF: 0.0211

Gnomad4 NFE exome AF: 0.0153

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0975 AC: 8240 AN: 84504 Hom.: 323 Cov.: 0 AF XY: 0.0968 AC XY: 3825 AN XY: 39502

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0782

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.129

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;