chr12-110436687-GA-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001278556.2(ARPC3):​c.253-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 807,002 control chromosomes in the GnomAD database, including 1 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 0.000047 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (1 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000467 AC: 4 AN: 85732 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000453

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000733

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000762 AC: 10 AN: 131236 Hom.: 0 AF XY: 0.0000973 AC XY: 7 AN XY: 71968

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000369

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000589

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 73 AN: 721270 Hom.: 1 Cov.: 24 AF XY: 0.000101 AC XY: 38 AN XY: 374806

Gnomad4 AFR exome AF: 0.0000768

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000522

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000181

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.0000319

GnomAD4 genome AF: 0.0000467 AC: 4 AN: 85732 Hom.: 0 Cov.: 0 AF XY: 0.0000500 AC XY: 2 AN XY: 39992

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000453

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000733

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;