rs751519228

Variant names:

• chr7-150293371-G-A
• rs751519228
• NM_001164458.2:c.94C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164458.2(ACTR3C):​c.94C>T​(p.Arg32Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,608,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12376723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2	c.94C>T	p.Arg32Cys	missense_variant	Exon 3 of 8	ENST00000683684.1	NP_001157930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1	c.94C>T	p.Arg32Cys	missense_variant	Exon 3 of 8		NM_001164458.2	ENSP00000507618.1

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151896 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 34 AN: 243470 AF XY: 0.0000839

Gnomad AFR exome AF: 0.000259

Gnomad AMR exome AF: 0.000442

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000825

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000309 AC: 45 AN: 1456196 Hom.: 0 Cov.: 33 AF XY: 0.0000221 AC XY: 16 AN XY: 723576

African (AFR) AF: 0.000419 AC: 14 AN: 33434

American (AMR) AF: 0.000362 AC: 16 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 84898

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108970

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome AF: 0.000119 AC: 18 AN: 151896 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74178

African (AFR) AF: 0.000290 AC: 12 AN: 41328

American (AMR) AF: 0.000262 AC: 4 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000162

ExAC AF: 0.0000906 AC: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94C>T (p.R32C) alteration is located in exon 3 (coding exon 2) of the ACTR3C gene. This alteration results from a C to T substitution at nucleotide position 94, causing the arginine (R) at amino acid position 32 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	30
DANN	Benign	0.89
DEOGEN2	Uncertain	0.50	D;.;.;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.6	M;.;.;.
PhyloP100		2.4
PROVEAN	Pathogenic	-4.8	D;D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.057	T;T;D;D
Sift4G	Uncertain	0.0030	D;D;.;D
Polyphen		0.18	B;.;.;.
Vest4		0.75
MutPred		0.54		Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);.;Loss of solvent accessibility (P = 0.0111);
MVP		0.67
MPC		0.72
ClinPred		0.34	T
GERP RS		0.85
Varity_R		0.21
gMVP		0.66
Mutation Taster		=85/15	polymorphism

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: rs751519228; hg19: chr7-149990460;