rs78661149

chr7-150286477-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001164458.2(ACTR3C):c.361C>T(p.Gln121Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 148,166 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.042 (205 hom., cov: 30)
  • Exomes 𝑓: 0.043 (2980 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTR3C NM_001164458.2 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0600

Genes affected

ACTR3C (HGNC:37282): (actin related protein 3C) Predicted to enable ATP binding activity. Predicted to contribute to actin filament binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Stoplost variant in NM_001164458.2 Downstream stopcodon found after 141 codons.
• BP6: Variant 7-150286477-G-A is Benign according to our data. Variant chr7-150286477-G-A is described in ClinVar as [Benign]. Clinvar id is 402338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR3C	NM_001164458.2	c.361C>T	p.Gln121Ter	stop_gained	5/8	ENST00000683684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR3C	ENST00000683684.1	c.361C>T	p.Gln121Ter	stop_gained	5/8		NM_001164458.2	P1

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6242 AN: 148052 Hom.: 203 Cov.: 30

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0575

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0696

Gnomad EAS AF: 0.00449

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0388

GnomAD3 exomes AF: 0.0495 AC: 12268 AN: 247772 Hom.: 478 AF XY: 0.0533 AC XY: 7128 AN XY: 133696

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.0197

Gnomad ASJ exome AF: 0.0506

Gnomad EAS exome AF: 0.00517

Gnomad SAS exome AF: 0.0900

Gnomad FIN exome AF: 0.0853

Gnomad NFE exome AF: 0.0530

Gnomad OTH exome AF: 0.0503

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0434 AC: 61001 AN: 1406730 Hom.: 2980 Cov.: 31 AF XY: 0.0455 AC XY: 31819 AN XY: 699942

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0517

Gnomad4 EAS exome AF: 0.00633

Gnomad4 SAS exome AF: 0.0940

Gnomad4 FIN exome AF: 0.0801

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0458

GnomAD4 genome AF: 0.0421 AC: 6244 AN: 148166 Hom.: 205 Cov.: 30 AF XY: 0.0430 AC XY: 3104 AN XY: 72186

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0696

Gnomad4 EAS AF: 0.00450

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0548

Gnomad4 OTH AF: 0.0395

Alfa AF: 0.0588 Hom.: 48

ExAC AF: 0.0558 AC: 6771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Pathogenic	0.17
Cadd	Pathogenic	36
Dann	Benign	0.95
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.051	N
MutationTaster	Benign	1.0	A;A
Vest4		0.24, 0.23
GERP RS		1.5

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

Publications

LitVar

Other links and lift over

dbSNP: rs78661149; hg19: chr7-149983566; COSMIC: COSV52740187;