7-150284764-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001164458.2(ACTR3C):c.553C>T(p.Pro185Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P185L) has been classified 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: 9.06

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR3C	NM_001164458.2	c.553C>T	p.Pro185Ser	missense_variant	6/8	ENST00000683684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR3C	ENST00000683684.1	c.553C>T	p.Pro185Ser	missense_variant	6/8		NM_001164458.2	P1
ACTR3C	ENST00000252071.8	c.553C>T	p.Pro185Ser	missense_variant	6/8	1		P1
ACTR3C	ENST00000478393.5	c.547C>T	p.Pro183Ser	missense_variant	5/6	1
ACTR3C	ENST00000539352.5	c.553C>T	p.Pro185Ser	missense_variant	5/5	5

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.553C>T (p.P185S) alteration is located in exon 6 (coding exon 5) of the ACTR3C gene. This alteration results from a C to T substitution at nucleotide position 553, causing the proline (P) at amino acid position 185 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.40	D
MutationTaster	Benign	0.86	D;D
PROVEAN	Benign	0.010	N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.99	.;D;.
Vest4		0.74, 0.73
MutPred		0.49		.;Gain of phosphorylation at P185 (P = 0.0478);Gain of phosphorylation at P185 (P = 0.0478);
MVP		0.84
MPC		0.35
ClinPred		0.96	D
GERP RS		2.2
Varity_R		0.077
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-149981853;