Genetic Variant ARPC3:c.253-8_253-5dupTTTT (chr12-110436687-G-GAAAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001278556.2(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
NM_001278556.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29

Publications

2 publications found

Variant links:

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 links:

ENSG00000258210 (HGNC:):

ENSG00000258210 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.253-8_253-5dupTTTT		splice_region intron	N/A	NP_001265485.1	O15145
	ARPC3	NM_001287222.2		c.253-8_253-5dupTTTT		splice_region intron	N/A	NP_001274151.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARPC3	ENST00000228825.12	TSL:1 MANE Select	c.253-5_253-4insTTTT	splice_region intron	N/A	ENSP00000228825.7	O15145
ARPC3	ENST00000888155.1		c.355-5_355-4insTTTT	splice_region intron	N/A	ENSP00000558214.1
ARPC3	ENST00000888156.1		c.313-5_313-4insTTTT	splice_region intron	N/A	ENSP00000558215.1

Frequencies

GnomAD3 genomes

AF:

0.0400

AC:

3417

AN:

85394

Hom.:

197

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00416

AC:

546

AN:

131236

AF XY:

0.00354

show subpopulations

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 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.:

Cov.:

AF XY:

0.00299

AC XY:

1119

AN XY:

374092

show subpopulations

African (AFR)

AF:

0.0504

AC:

642

AN:

12746

American (AMR)

AF:

0.00286

AC:

AN:

33542

Ashkenazi Jewish (ASJ)

AF:

0.00897

AC:

136

AN:

15170

East Asian (EAS)

AF:

0.000329

AC:

AN:

24324

South Asian (SAS)

AF:

0.00221

AC:

122

AN:

55082

European-Finnish (FIN)

AF:

0.000834

AC:

AN:

32360

Middle Eastern (MID)

AF:

0.00393

AC:

AN:

2800

European-Non Finnish (NFE)

AF:

0.00196

AC:

1004

AN:

512670

Other (OTH)

AF:

0.00585

AC:

183

AN:

31296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

181

271

362

452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0401

AC:

3427

AN:

85412

Hom.:

199

Cov.:

AF XY:

0.0399

AC XY:

1592

AN XY:

39880

show subpopulations

African (AFR)

AF:

0.120

AC:

2931

AN:

24432

American (AMR)

AF:

0.0207

AC:

157

AN:

7576

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

AN:

2176

East Asian (EAS)

AF:

0.00200

AC:

AN:

2496

South Asian (SAS)

AF:

0.00628

AC:

AN:

2548

European-Finnish (FIN)

AF:

0.00406

AC:

AN:

3448

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.00437

AC:

179

AN:

40916

Other (OTH)

AF:

0.0315

AC:

AN:

1080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

104

208

311

415

519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0147

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-110436687-GA-GAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over