7-150286516-C-A

Variant names:

• chr7-150286516-C-A
• rs780988364
• NM_001164458.2:c.322G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001164458.2(ACTR3C):​c.322G>T​(p.Asp108Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D108H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

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.322G>T	p.Asp108Tyr	missense	Exon 5 of 8	NP_001157930.1	Q9C0K3-1
	ACTR3C	NM_001164459.2		c.322G>T	p.Asp108Tyr	missense	Exon 5 of 8	NP_001157931.1	Q9C0K3-1
	ACTR3C	NM_001351028.2		c.-220G>T		5_prime_UTR	Exon 5 of 10	NP_001337957.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3C	ENST00000683684.1	MANE Select	c.322G>T	p.Asp108Tyr	missense	Exon 5 of 8	ENSP00000507618.1	Q9C0K3-1
	ACTR3C	ENST00000252071.8	TSL:1	c.322G>T	p.Asp108Tyr	missense	Exon 5 of 8	ENSP00000252071.4	Q9C0K3-1
	ACTR3C	ENST00000478393.5	TSL:1	c.316G>T	p.Asp106Tyr	missense	Exon 4 of 6	ENSP00000417426.1	H7C4J1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.0044	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		4.4
PROVEAN	Pathogenic	-8.6	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.70		Gain of ubiquitination at K111 (P = 0.0671)
MVP		0.54
MPC		1.2
ClinPred		1.0	D
GERP RS		2.5
Varity_R		0.93
gMVP		0.82
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -7
DS_AL_spliceai		0.25		Position offset: 24

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

Other links and lift over

dbSNP: rs780988364; hg19: chr7-149983605;