12-110436687-G-GAAAA

Position:

• chr12-110436687-G-GAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000228825.12(ARPC3):​c.253-8_253-5dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 805,402 control chromosomes in the GnomAD database, including 270 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (199 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (71 hom.)
• Consequence: ARPC3 ENST00000228825.12 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ARPC3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-110436687-G-GAAAA is Benign according to our data. Variant chr12-110436687-G-GAAAA is described in ClinVar as [Benign]. Clinvar id is 777238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC3	NM_001278556.2	c.253-8_253-5dupTTTT		splice_region_variant, intron_variant		ENST00000228825.12	NP_001265485.1
ARPC3	NM_001287222.2	c.253-8_253-5dupTTTT		splice_region_variant, intron_variant			NP_001274151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC3	ENST00000228825.12	c.253-8_253-5dupTTTT		splice_region_variant, intron_variant		1	NM_001278556.2	ENSP00000228825.7

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 3417 AN: 85394 Hom.: 197 Cov.: 0

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.00200

Gnomad SAS AF: 0.00665

Gnomad FIN AF: 0.00406

Gnomad MID AF: 0.0147

Gnomad NFE AF: 0.00437

Gnomad OTH AF: 0.0316

GnomAD3 exomes AF: 0.00416 AC: 546 AN: 131236 Hom.: 16 AF XY: 0.00354 AC XY: 255 AN XY: 71968

Gnomad AFR exome AF: 0.0474

Gnomad AMR exome AF: 0.00294

Gnomad ASJ exome AF: 0.00702

Gnomad EAS exome AF: 0.000195

Gnomad SAS exome AF: 0.00165

Gnomad FIN exome AF: 0.000595

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00447

GnomAD4 exome AF: 0.00310 AC: 2229 AN: 719990 Hom.: 71 Cov.: 24 AF XY: 0.00299 AC XY: 1119 AN XY: 374092

Gnomad4 AFR exome AF: 0.0504

Gnomad4 AMR exome AF: 0.00286

Gnomad4 ASJ exome AF: 0.00897

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.000834

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00585

GnomAD4 genome AF: 0.0401 AC: 3427 AN: 85412 Hom.: 199 Cov.: 0 AF XY: 0.0399 AC XY: 1592 AN XY: 39880

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.00200

Gnomad4 SAS AF: 0.00628

Gnomad4 FIN AF: 0.00406

Gnomad4 NFE AF: 0.00437

Gnomad4 OTH AF: 0.0315

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 05, 2018

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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;