12-110436687-GA-GAAAAAAAAA

Variant names:

• chr12-110436687-G-GAAAAAAAA
• rs59861890
• NM_001278556.2:c.253-12_253-5dupTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001278556.2(ARPC3):​c.253-12_253-5dupTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.253-12_253-5dupTTTTTTTT		splice_region intron	N/A	NP_001265485.1	O15145
	ARPC3	NM_001287222.2		c.253-12_253-5dupTTTTTTTT		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_253-4insTTTTTTTT		splice_region intron	N/A	ENSP00000228825.7	O15145
	ARPC3	ENST00000888155.1		c.355-5_355-4insTTTTTTTT		splice_region intron	N/A	ENSP00000558214.1
	ARPC3	ENST00000888156.1		c.313-5_313-4insTTTTTTTT		splice_region intron	N/A	ENSP00000558215.1

Frequencies

GnomAD3 genomes AF: 0.0000233 AC: 2 AN: 85732 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000811

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 721302 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 374818

African (AFR) AF: 0.00 AC: 0 AN: 13022

American (AMR) AF: 0.00 AC: 0 AN: 33660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15316

East Asian (EAS) AF: 0.00 AC: 0 AN: 24338

South Asian (SAS) AF: 0.00 AC: 0 AN: 55184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2802

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 513178

Other (OTH) AF: 0.00 AC: 0 AN: 31390

GnomAD4 genome AF: 0.0000233 AC: 2 AN: 85758 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40036

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

African (AFR) AF: 0.0000809 AC: 2 AN: 24716

American (AMR) AF: 0.00 AC: 0 AN: 7578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2206

East Asian (EAS) AF: 0.00 AC: 0 AN: 2500

South Asian (SAS) AF: 0.00 AC: 0 AN: 2550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40932

Other (OTH) AF: 0.00 AC: 0 AN: 1084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

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;