3-9797667-T-C

Variant names:

• chr3-9797667-T-C
• NM_005718.5:c.12T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_005718.5(ARPC4):​c.12T>C​(p.Thr4Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARPC4 NM_005718.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.578
• Publications: 0 publications found

Genes affected

ARPC4 (HGNC:707): (actin related protein 2/3 complex subunit 4) This gene encodes one of seven subunits of the human Arp2/3 protein complex. This complex controls actin polymerization in cells and has been conserved throughout eukaryotic evolution. This gene encodes the p20 subunit, which is necessary for actin nucleation and high-affinity binding to F-actin. Alternative splicing results in multiple transcript variants. Naturally occurring read-through transcription exists between this gene and the downstream tubulin tyrosine ligase-like family, member 3 (TTLL3), which results in the production of a fusion protein. [provided by RefSeq, Nov 2010]

ARPC4-TTLL3 (HGNC:38830): (ARPC4-TTLL3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ARPC4 (actin related protein 2/3 complex, subunit 4) and TTLL3 (tubulin tyrosine ligase-like family, member 3) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.025).
• BP6: Variant 3-9797667-T-C is Benign according to our data. Variant chr3-9797667-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3769331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.578 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005718.5. 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
	ARPC4	NM_005718.5	MANE Select	c.12T>C	p.Thr4Thr	synonymous	Exon 2 of 6	NP_005709.1	P59998-1
	ARPC4-TTLL3	NM_001198793.1		c.12T>C	p.Thr4Thr	synonymous	Exon 2 of 12	NP_001185722.1	A0A0A6YYG9
	ARPC4	NM_001198780.3		c.69T>C	p.Thr23Thr	synonymous	Exon 2 of 6	NP_001185709.1	P59998-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC4	ENST00000397261.8	TSL:1 MANE Select	c.12T>C	p.Thr4Thr	synonymous	Exon 2 of 6	ENSP00000380431.2	P59998-1
	ARPC4-TTLL3	ENST00000397256.5	TSL:5	c.12T>C	p.Thr4Thr	synonymous	Exon 2 of 12	ENSP00000380427.1
	ARPC4	ENST00000433034.1	TSL:3	c.69T>C	p.Thr23Thr	synonymous	Exon 2 of 6	ENSP00000388169.1	P59998-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.58
PromoterAI		0.0073	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr3-9839351;