14-58215230-C-G

Position:

• chr14-58215230-C-G

Variant summary

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

The NM_018477.3(ACTR10):​c.544C>G​(p.Gln182Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACTR10 NM_018477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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

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=0.30128825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR10	NM_018477.3	c.544C>G	p.Gln182Glu	missense_variant	7/13	ENST00000254286.9	NP_060947.1
ACTR10	XM_011536960.2	c.544C>G	p.Gln182Glu	missense_variant	7/13		XP_011535262.1
ACTR10	XM_011536961.2	c.544C>G	p.Gln182Glu	missense_variant	7/12		XP_011535263.1
ACTR10	XM_047431587.1	c.-51C>G		5_prime_UTR_variant	2/8		XP_047287543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR10	ENST00000254286.9	c.544C>G	p.Gln182Glu	missense_variant	7/13	1	NM_018477.3	ENSP00000254286.4
ACTR10	ENST00000554402.6	n.541C>G		non_coding_transcript_exon_variant	7/14	1		ENSP00000477173.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

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

Aug 20, 2024

The c.544C>G (p.Q182E) alteration is located in exon 7 (coding exon 7) of the ACTR10 gene. This alteration results from a C to G substitution at nucleotide position 544, causing the glutamine (Q) at amino acid position 182 to be replaced by a glutamic acid (E). 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	0.086
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.037
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.046	T
MutationAssessor	Benign	0.52	N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.18	N
REVEL	Uncertain	0.39
Sift	Benign	0.55	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.38
MutPred		0.36		Gain of glycosylation at T187 (P = 0.132);
MVP		0.90
MPC		0.32
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr14-58681948; COSMIC: COSV99581246; COSMIC: COSV99581246;