12-110436687-GA-GAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.0963 is higher than 0.05.

Transcripts

RefSeq

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

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

GnomAD3 exomes AF: 0.0213 AC: 2801 AN: 131236 Hom.: 320 AF XY: 0.0206 AC XY: 1483 AN XY: 71968

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 SAS exome AF: 0.0295

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

Gnomad4 AFR exome AF: 0.0980

Gnomad4 AMR exome AF: 0.0223

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.00773

Gnomad4 SAS exome AF: 0.0246

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0204

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

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0574

Gnomad4 EAS AF: 0.0437

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0331

Gnomad4 OTH AF: 0.0536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs59861890; hg19: chr12-110874492;