chr7-150286477-G-A

Variant names:

• chr7-150286477-G-A
• rs78661149
• NM_001164458.2:c.361C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001164458.2(ACTR3C):​c.361C>T​(p.Gln121*) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0600
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• 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_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 205 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2	c.361C>T	p.Gln121*	stop_gained	Exon 5 of 8	ENST00000683684.1	NP_001157930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1	c.361C>T	p.Gln121*	stop_gained	Exon 5 of 8		NM_001164458.2	ENSP00000507618.1

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

GnomAD2 exomes AF: 0.0495 AC: 12268 AN: 247772 AF XY: 0.0533

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 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

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

African (AFR) AF: 0.0152 AC: 504 AN: 33214

American (AMR) AF: 0.0193 AC: 858 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.0517 AC: 1308 AN: 25304

East Asian (EAS) AF: 0.00633 AC: 251 AN: 39622

South Asian (SAS) AF: 0.0940 AC: 7831 AN: 83338

European-Finnish (FIN) AF: 0.0801 AC: 4204 AN: 52464

Middle Eastern (MID) AF: 0.0639 AC: 358 AN: 5600

European-Non Finnish (NFE) AF: 0.0404 AC: 43007 AN: 1064270

Other (OTH) AF: 0.0458 AC: 2680 AN: 58504

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

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

African (AFR) AF: 0.0166 AC: 660 AN: 39814

American (AMR) AF: 0.0257 AC: 387 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.0696 AC: 238 AN: 3422

East Asian (EAS) AF: 0.00450 AC: 23 AN: 5106

South Asian (SAS) AF: 0.0788 AC: 355 AN: 4506

European-Finnish (FIN) AF: 0.0759 AC: 759 AN: 10000

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0548 AC: 3673 AN: 66996

Other (OTH) AF: 0.0395 AC: 81 AN: 2052

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0588 Hom.: 48

ExAC AF: 0.0558 AC: 6771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		0.060
Vest4		0.24, 0.23
GERP RS		1.5
Mutation Taster		=189/11	polymorphism (auto)

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

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