ACTR3C p.Met164Ile

Variant names:

• chr7-150284825-C-A
• NM_001164458.2:c.492G>T
• ACTR3C p.Met164Ile

Your query was ambiguous. Multiple possible variants found:

• chr7-150284825-C-A
• chr7-150284825-C-G
• chr7-150284825-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164458.2(ACTR3C):​c.492G>T​(p.Met164Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14644182).

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.492G>T	p.Met164Ile	missense	Exon 6 of 8	NP_001157930.1	Q9C0K3-1
	ACTR3C	NM_001351028.2		c.-50G>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 10	NP_001337957.1
	ACTR3C	NM_001164459.2		c.492G>T	p.Met164Ile	missense	Exon 6 of 8	NP_001157931.1	Q9C0K3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3C	ENST00000683684.1	MANE Select	c.492G>T	p.Met164Ile	missense	Exon 6 of 8	ENSP00000507618.1	Q9C0K3-1
	ACTR3C	ENST00000252071.8	TSL:1	c.492G>T	p.Met164Ile	missense	Exon 6 of 8	ENSP00000252071.4	Q9C0K3-1
	ACTR3C	ENST00000478393.5	TSL:1	c.486G>T	p.Met162Ile	missense	Exon 5 of 6	ENSP00000417426.1	H7C4J1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	23
DANN	Benign	0.92
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.98	L
PhyloP100		0.47
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.023
Sift	Benign	0.25	T
Sift4G	Benign	0.14	T
Varity_R		0.087
gMVP		0.58
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-149981914;