7-150284823-T-C

Variant names:

• chr7-150284823-T-C
• NM_001164458.2:c.494A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164458.2(ACTR3C):​c.494A>G​(p.Glu165Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31339788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2	c.494A>G	p.Glu165Gly	missense_variant	Exon 6 of 8	ENST00000683684.1	NP_001157930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1	c.494A>G	p.Glu165Gly	missense_variant	Exon 6 of 8		NM_001164458.2	ENSP00000507618.1
ACTR3C	ENST00000252071.8	c.494A>G	p.Glu165Gly	missense_variant	Exon 6 of 8	1		ENSP00000252071.4
ACTR3C	ENST00000478393.5	c.488A>G	p.Glu163Gly	missense_variant	Exon 5 of 6	1		ENSP00000417426.1
ACTR3C	ENST00000539352.5	c.494A>G	p.Glu165Gly	missense_variant	Exon 5 of 5	5		ENSP00000440990.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.494A>G (p.E165G) alteration is located in exon 6 (coding exon 5) of the ACTR3C gene. This alteration results from a A to G substitution at nucleotide position 494, causing the glutamic acid (E) at amino acid position 165 to be replaced by a glycine (G). 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	Benign	0.15
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0050	.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.94	.;L;.
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.16	.;B;.
Vest4		0.60, 0.46
MutPred		0.33		.;Loss of solvent accessibility (P = 0.0299);Loss of solvent accessibility (P = 0.0299);
MVP		0.80
MPC		0.50
ClinPred		0.46	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-149981912;