Genetic Variant ARPC3:c.253-11_253-5dupTTTTTTT (chr12-110436687-G-GAAAAAAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001278556.2(ARPC3):c.253-11_253-5dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 807,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000097 ( 0 hom. )

Consequence

ARPC3
NM_001278556.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

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 made for transcript

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 link	c.253-11_253-5dupTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000228825.12	NP_001265485.1	O15145
ARPC3	NM_001287222.2 link	c.253-11_253-5dupTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 6		NP_001274151.1	O15145

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC3	ENST00000228825.12 link	c.253-5_253-4insTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_001278556.2	ENSP00000228825.7		O15145

Frequencies

GnomAD3 genomes

AF:

0.0000467

AC:

AN:

85726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000970

AC:

AN:

721284

Hom.:

Cov.:

AF XY:

0.00000534

AC XY:

AN XY:

374800

show subpopulations

Gnomad4 AFR exome

AF:

0.0000768

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000653

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000974

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000466

AC:

AN:

85752

Hom.:

Cov.:

AF XY:

0.0000500

AC XY:

AN XY:

40034

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

12-110436687-GA-GAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over