14-58202887-G-A

Variant names:

• chr14-58202887-G-A
• rs1320026758
• NM_018477.3:c.110G>A

Variant summary

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

The NM_018477.3(ACTR10):​c.110G>A​(p.Cys37Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ACTR10 NM_018477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.96

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR10	NM_018477.3	c.110G>A	p.Cys37Tyr	missense_variant	Exon 2 of 13	ENST00000254286.9	NP_060947.1
ACTR10	XM_011536960.2	c.110G>A	p.Cys37Tyr	missense_variant	Exon 2 of 13		XP_011535262.1
ACTR10	XM_011536961.2	c.110G>A	p.Cys37Tyr	missense_variant	Exon 2 of 12		XP_011535263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR10	ENST00000254286.9	c.110G>A	p.Cys37Tyr	missense_variant	Exon 2 of 13	1	NM_018477.3	ENSP00000254286.4
ACTR10	ENST00000554402.6	n.107G>A		non_coding_transcript_exon_variant	Exon 2 of 14	1		ENSP00000477173.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246982 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133530

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000339

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456136 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110G>A (p.C37Y) alteration is located in exon 2 (coding exon 2) of the ACTR10 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the cysteine (C) at amino acid position 37 to be replaced by a tyrosine (Y). 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	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	22
DANN	Benign	0.76
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.64
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.47	P
Vest4		0.70
MutPred		0.37		Loss of sheet (P = 0.0817);
MVP		0.99
MPC		0.92
ClinPred		0.73	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs1320026758; hg19: chr14-58669605;