12-110436687-GA-GAA

Variant names:

• chr12-110436687-G-GA
• rs59861890
• NM_001278556.2:c.253-5dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001278556.2(ARPC3):​c.253-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 803,604 control chromosomes in the GnomAD database, including 1,428 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.056 (210 hom., cov: 0)
  • Exomes 𝑓: 0.016 (1218 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 = 0.0963 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.253-5dupT		splice_region intron	N/A	NP_001265485.1	O15145
	ARPC3	NM_001287222.2		c.253-5dupT		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_253-4insT		splice_region intron	N/A	ENSP00000228825.7	O15145
	ARPC3	ENST00000888155.1		c.355-5_355-4insT		splice_region intron	N/A	ENSP00000558214.1
	ARPC3	ENST00000888156.1		c.313-5_313-4insT		splice_region intron	N/A	ENSP00000558215.1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 4790 AN: 85406 Hom.: 210 Cov.: 0

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.0919

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0574

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0980

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0557

GnomAD2 exomes AF: 0.0213 AC: 2801 AN: 131236 AF XY: 0.0206

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.0265

Gnomad ASJ exome AF: 0.0247

Gnomad EAS exome AF: 0.00516

Gnomad FIN exome AF: 0.0202

Gnomad NFE exome AF: 0.0130

Gnomad OTH exome AF: 0.0208

GnomAD4 exome AF: 0.0156 AC: 11205 AN: 718176 Hom.: 1218 Cov.: 24 AF XY: 0.0156 AC XY: 5830 AN XY: 373056

African (AFR) AF: 0.0980 AC: 1257 AN: 12828

American (AMR) AF: 0.0223 AC: 746 AN: 33522

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 380 AN: 15196

East Asian (EAS) AF: 0.00773 AC: 187 AN: 24202

South Asian (SAS) AF: 0.0246 AC: 1342 AN: 54624

European-Finnish (FIN) AF: 0.0105 AC: 340 AN: 32292

Middle Eastern (MID) AF: 0.0330 AC: 92 AN: 2788

European-Non Finnish (NFE) AF: 0.0122 AC: 6223 AN: 511496

Other (OTH) AF: 0.0204 AC: 638 AN: 31228

GnomAD4 genome AF: 0.0560 AC: 4786 AN: 85428 Hom.: 210 Cov.: 0 AF XY: 0.0569 AC XY: 2272 AN XY: 39896

African (AFR) AF: 0.0996 AC: 2446 AN: 24570

American (AMR) AF: 0.0557 AC: 420 AN: 7546

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 126 AN: 2194

East Asian (EAS) AF: 0.0437 AC: 109 AN: 2492

South Asian (SAS) AF: 0.0587 AC: 149 AN: 2538

European-Finnish (FIN) AF: 0.0162 AC: 56 AN: 3448

Middle Eastern (MID) AF: 0.105 AC: 20 AN: 190

European-Non Finnish (NFE) AF: 0.0331 AC: 1352 AN: 40824

Other (OTH) AF: 0.0536 AC: 58 AN: 1082

Alfa AF: 0.0169 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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs59861890; hg19: chr12-110874492;