12-110436687-GA-GAAAAAAA

Variant names:

• chr12-110436687-G-GAAAAAA
• rs59861890
• NM_001278556.2:c.253-10_253-5dupTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001278556.2(ARPC3):​c.253-10_253-5dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 806,810 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 0)
  • Exomes 𝑓: 0.000096 (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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC3	NM_001278556.2	c.253-10_253-5dupTTTTTT		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000228825.12	NP_001265485.1
ARPC3	NM_001287222.2	c.253-10_253-5dupTTTTTT		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_253-4insTTTTTT		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_001278556.2	ENSP00000228825.7

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 350 AN: 85606 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00291

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: 0.000244

Gnomad OTH AF: 0.00278

GnomAD4 exome AF: 0.0000957 AC: 69 AN: 721176 Hom.: 1 Cov.: 24 AF XY: 0.0000961 AC XY: 36 AN XY: 374756

Gnomad4 AFR exome AF: 0.00216

Gnomad4 AMR exome AF: 0.000178

Gnomad4 ASJ exome AF: 0.000131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000487

Gnomad4 OTH exome AF: 0.000255

GnomAD4 genome AF: 0.00410 AC: 351 AN: 85634 Hom.: 4 Cov.: 0 AF XY: 0.00338 AC XY: 135 AN XY: 39986

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00291

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.00277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;