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. The variant received -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
• 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 (AFR) allele frequency at 95% confidence interval = 0.123 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.253-7_253-5dupTTT		splice_region intron	N/A	NP_001265485.1	O15145
	ARPC3	NM_001287222.2		c.253-7_253-5dupTTT		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_253-4insTTT		splice_region intron	N/A	ENSP00000228825.7	O15145
	ARPC3	ENST00000888155.1		c.355-5_355-4insTTT		splice_region intron	N/A	ENSP00000558214.1
	ARPC3	ENST00000888156.1		c.313-5_313-4insTTT		splice_region intron	N/A	ENSP00000558215.1

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

GnomAD2 exomes AF: 0.0323 AC: 4245 AN: 131236 AF XY: 0.0322

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 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

African (AFR) AF: 0.0655 AC: 830 AN: 12670

American (AMR) AF: 0.0217 AC: 722 AN: 33276

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 1467 AN: 14932

East Asian (EAS) AF: 0.00605 AC: 147 AN: 24278

South Asian (SAS) AF: 0.0394 AC: 2131 AN: 54150

European-Finnish (FIN) AF: 0.0258 AC: 828 AN: 32052

Middle Eastern (MID) AF: 0.0442 AC: 121 AN: 2740

European-Non Finnish (NFE) AF: 0.0358 AC: 18135 AN: 507204

Other (OTH) AF: 0.0442 AC: 1363 AN: 30870

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

African (AFR) AF: 0.126 AC: 3071 AN: 24312

American (AMR) AF: 0.0773 AC: 582 AN: 7528

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 402 AN: 2194

East Asian (EAS) AF: 0.00920 AC: 23 AN: 2500

South Asian (SAS) AF: 0.0806 AC: 205 AN: 2542

European-Finnish (FIN) AF: 0.0883 AC: 303 AN: 3432

Middle Eastern (MID) AF: 0.151 AC: 28 AN: 186

European-Non Finnish (NFE) AF: 0.103 AC: 4194 AN: 40734

Other (OTH) AF: 0.116 AC: 125 AN: 1074

Alfa AF: 0.0285 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;