chr12-110436687-G-GAAAAA

Variant names:

• chr12-110436687-G-GAAAAA
• rs59861890
• NM_001278556.2:c.253-9_253-5dupTTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001278556.2(ARPC3):​c.253-9_253-5dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 803,946 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (13 hom., cov: 0)
  • Exomes 𝑓: 0.00093 (6 hom.)
• Consequence: ARPC3 NM_001278556.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-110436687-G-GAAAAA is Benign according to our data. Variant chr12-110436687-G-GAAAAA is described in ClinVar as Benign. ClinVar VariationId is 785427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0136 (1157/85374) while in subpopulation AFR AF = 0.0177 (435/24598). AF 95% confidence interval is 0.0163. There are 13 homozygotes in GnomAd4. There are 503 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.253-9_253-5dupTTTTT		splice_region intron	N/A	NP_001265485.1	O15145
	ARPC3	NM_001287222.2		c.253-9_253-5dupTTTTT		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_253-4insTTTTT		splice_region intron	N/A	ENSP00000228825.7	O15145
	ARPC3	ENST00000888155.1		c.355-5_355-4insTTTTT		splice_region intron	N/A	ENSP00000558214.1
	ARPC3	ENST00000888156.1		c.313-5_313-4insTTTTT		splice_region intron	N/A	ENSP00000558215.1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 1159 AN: 85346 Hom.: 13 Cov.: 0

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00689

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.000290

Gnomad MID AF: 0.00990

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0224

GnomAD2 exomes AF: 0.000617 AC: 81 AN: 131236 AF XY: 0.000445

Gnomad AFR exome AF: 0.00496

Gnomad AMR exome AF: 0.000362

Gnomad ASJ exome AF: 0.00111

Gnomad EAS exome AF: 0.0000974

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.000596

GnomAD4 exome AF: 0.000931 AC: 669 AN: 718572 Hom.: 6 Cov.: 24 AF XY: 0.00102 AC XY: 379 AN XY: 373242

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

African (AFR) AF: 0.00542 AC: 70 AN: 12918

American (AMR) AF: 0.000715 AC: 24 AN: 33564

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 28 AN: 15208

East Asian (EAS) AF: 0.0000411 AC: 1 AN: 24338

South Asian (SAS) AF: 0.000840 AC: 46 AN: 54770

European-Finnish (FIN) AF: 0.000154 AC: 5 AN: 32372

Middle Eastern (MID) AF: 0.000358 AC: 1 AN: 2792

European-Non Finnish (NFE) AF: 0.000888 AC: 454 AN: 511372

Other (OTH) AF: 0.00128 AC: 40 AN: 31238

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0136 AC: 1157 AN: 85374 Hom.: 13 Cov.: 0 AF XY: 0.0126 AC XY: 503 AN XY: 39878

African (AFR) AF: 0.0177 AC: 435 AN: 24598

American (AMR) AF: 0.00688 AC: 52 AN: 7558

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 32 AN: 2200

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

South Asian (SAS) AF: 0.0138 AC: 35 AN: 2544

European-Finnish (FIN) AF: 0.000290 AC: 1 AN: 3450

Middle Eastern (MID) AF: 0.0106 AC: 2 AN: 188

European-Non Finnish (NFE) AF: 0.0139 AC: 567 AN: 40710

Other (OTH) AF: 0.0223 AC: 24 AN: 1076

Alfa AF: 0.00103 Hom.: 27

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=97/3	polymorphism

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;