7-150295263-T-C

Variant names:

• chr7-150295263-T-C
• rs191789394
• NM_001164458.2:c.34A>G

Variant summary

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

The NM_001164458.2(ACTR3C):​c.34A>G​(p.Ile12Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,613,982 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. I12T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• 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=0.18053597).

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.34A>G	p.Ile12Val	missense	Exon 2 of 8	NP_001157930.1	Q9C0K3-1
	ACTR3C	NM_001164459.2		c.34A>G	p.Ile12Val	missense	Exon 2 of 8	NP_001157931.1	Q9C0K3-1
	ACTR3C	NM_001351028.2		c.-508A>G		5_prime_UTR	Exon 2 of 10	NP_001337957.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3C	ENST00000683684.1	MANE Select	c.34A>G	p.Ile12Val	missense	Exon 2 of 8	ENSP00000507618.1	Q9C0K3-1
	ACTR3C	ENST00000252071.8	TSL:1	c.34A>G	p.Ile12Val	missense	Exon 2 of 8	ENSP00000252071.4	Q9C0K3-1
	ACTR3C	ENST00000478393.5	TSL:1	c.147+43A>G		intron	N/A	ENSP00000417426.1	H7C4J1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00109

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000558 AC: 14 AN: 251102 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000862

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461628 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727116

African (AFR) AF: 0.000657 AC: 22 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111806

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74502

African (AFR) AF: 0.00108 AC: 45 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.000302

ESP6500AA AF: 0.00145 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

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	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	1.7	L
PhyloP100		5.6
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.43
Sift	Benign	0.24	T
Sift4G	Benign	0.69	T
Polyphen		0.98	D
Vest4		0.63
MVP		0.81
MPC		0.75
ClinPred		0.13	T
GERP RS		1.6
PromoterAI		-0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.47
Mutation Taster		=82/18	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: rs191789394; hg19: chr7-149992352;