chr14-58215244-C-A

Variant names:

• chr14-58215244-C-A
• NM_018477.3:c.558C>A

Variant summary

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

The NM_018477.3(ACTR10):​c.558C>A​(p.Asp186Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACTR10 NM_018477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.262
• Publications: 0 publications found

Genes affected

ACTR10 (HGNC:17372): (actin related protein 10) Predicted to be involved in retrograde axonal transport of mitochondrion. Predicted to be located in cytosol; extracellular region; and secretory granule. Predicted to be part of dynactin complex. [provided by Alliance of Genome Resources, Apr 2022]

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018477.3. 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
	ACTR10	NM_018477.3	MANE Select	c.558C>A	p.Asp186Glu	missense	Exon 7 of 13	NP_060947.1	Q9NZ32

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR10	ENST00000254286.9	TSL:1 MANE Select	c.558C>A	p.Asp186Glu	missense	Exon 7 of 13	ENSP00000254286.4	Q9NZ32
	ACTR10	ENST00000554402.6	TSL:1	n.555C>A		non_coding_transcript_exon	Exon 7 of 14	ENSP00000477173.1	V9GYX7
	ACTR10	ENST00000557711.5	TSL:1	n.705C>A		non_coding_transcript_exon	Exon 2 of 8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

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	0.24
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.26
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.15	N
REVEL	Uncertain	0.49
Sift	Benign	0.29	T
Sift4G	Benign	0.35	T
Polyphen		0.021	B
Vest4		0.73
MutPred		0.53		Gain of disorder (P = 0.0715)
MVP		0.79
MPC		0.29
ClinPred		0.35	T
GERP RS		3.9
Varity_R		0.079
gMVP		0.41
Mutation Taster		=77/23	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

Other links and lift over

hg19: chr14-58681962;