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. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC3	NM_001278556.2	MANE Select	c.253-6_253-5dupTT		splice_region intron	N/A	NP_001265485.1	O15145
	ARPC3	NM_001287222.2		c.253-6_253-5dupTT		splice_region intron	N/A	NP_001274151.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC3	ENST00000228825.12	TSL:1 MANE Select	c.253-5_253-4insTT		splice_region intron	N/A	ENSP00000228825.7	O15145
	ARPC3	ENST00000888155.1		c.355-5_355-4insTT		splice_region intron	N/A	ENSP00000558214.1
	ARPC3	ENST00000888156.1		c.313-5_313-4insTT		splice_region intron	N/A	ENSP00000558215.1

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

GnomAD2 exomes AF: 0.0126 AC: 1656 AN: 131236 AF XY: 0.0125

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0382 AC: 490 AN: 12824

American (AMR) AF: 0.0106 AC: 355 AN: 33402

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 295 AN: 15118

East Asian (EAS) AF: 0.0106 AC: 255 AN: 24148

South Asian (SAS) AF: 0.0209 AC: 1136 AN: 54226

European-Finnish (FIN) AF: 0.0211 AC: 675 AN: 32060

Middle Eastern (MID) AF: 0.0206 AC: 57 AN: 2772

European-Non Finnish (NFE) AF: 0.0153 AC: 7773 AN: 509262

Other (OTH) AF: 0.0199 AC: 618 AN: 31070

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0780 AC: 1909 AN: 24490

American (AMR) AF: 0.0980 AC: 733 AN: 7480

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 244 AN: 2176

East Asian (EAS) AF: 0.0782 AC: 194 AN: 2480

South Asian (SAS) AF: 0.112 AC: 282 AN: 2512

European-Finnish (FIN) AF: 0.110 AC: 378 AN: 3426

Middle Eastern (MID) AF: 0.130 AC: 24 AN: 184

European-Non Finnish (NFE) AF: 0.107 AC: 4279 AN: 40134

Other (OTH) AF: 0.129 AC: 139 AN: 1078

Alfa AF: 0.0172 Hom.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs59861890; hg19: chr12-110874492;