chr7-150289487-G-A

Variant names:

• chr7-150289487-G-A
• rs1245261886
• NM_001164458.2:c.260C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001164458.2(ACTR3C):​c.260C>T​(p.Pro87Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,590,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.06
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164458.2. 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
	ACTR3C	NM_001164458.2	MANE Select	c.260C>T	p.Pro87Leu	missense	Exon 4 of 8	NP_001157930.1	Q9C0K3-1
	ACTR3C	NM_001164459.2		c.260C>T	p.Pro87Leu	missense	Exon 4 of 8	NP_001157931.1	Q9C0K3-1
	ACTR3C	NM_001351028.2		c.-282C>T		5_prime_UTR	Exon 4 of 10	NP_001337957.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3C	ENST00000683684.1	MANE Select	c.260C>T	p.Pro87Leu	missense	Exon 4 of 8	ENSP00000507618.1	Q9C0K3-1
	ACTR3C	ENST00000252071.8	TSL:1	c.260C>T	p.Pro87Leu	missense	Exon 4 of 8	ENSP00000252071.4	Q9C0K3-1
	ACTR3C	ENST00000478393.5	TSL:1	c.254C>T	p.Pro85Leu	missense	Exon 3 of 6	ENSP00000417426.1	H7C4J1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150866 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000987 AC: 2 AN: 202708 AF XY: 0.00000921

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000219

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000535 AC: 77 AN: 1439568 Hom.: 0 Cov.: 31 AF XY: 0.0000462 AC XY: 33 AN XY: 713598

African (AFR) AF: 0.00 AC: 0 AN: 32326

American (AMR) AF: 0.0000233 AC: 1 AN: 42940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25372

East Asian (EAS) AF: 0.00 AC: 0 AN: 38606

South Asian (SAS) AF: 0.00 AC: 0 AN: 81312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.0000663 AC: 73 AN: 1101680

Other (OTH) AF: 0.0000504 AC: 3 AN: 59524

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150866 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73610

African (AFR) AF: 0.00 AC: 0 AN: 40622

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10500

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000868 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		9.1
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.39		Loss of disorder (P = 0.0236)
MVP		0.53
MPC		3.1
ClinPred		0.99	D
GERP RS		2.2
Varity_R		0.79
gMVP		0.61
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1245261886; hg19: chr7-149986576;