14-58200284-G-T

Position:

• chr14-58200284-G-T

Variant summary

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

The NM_018477.3(ACTR10):​c.67G>T​(p.Ala23Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000443 in 1,355,800 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: 0.0000044 (0 hom.)
• Consequence: ACTR10 NM_018477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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/exons	MANE	Protein	UniProt
ACTR10	NM_018477.3	c.67G>T	p.Ala23Ser	missense_variant	1/13	ENST00000254286.9	NP_060947.1
ACTR10	XM_011536960.2	c.67G>T	p.Ala23Ser	missense_variant	1/13		XP_011535262.1
ACTR10	XM_011536961.2	c.67G>T	p.Ala23Ser	missense_variant	1/12		XP_011535263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR10	ENST00000254286.9	c.67G>T	p.Ala23Ser	missense_variant	1/13	1	NM_018477.3	ENSP00000254286	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000443 AC: 6 AN: 1355800 Hom.: 0 Cov.: 30 AF XY: 0.00000445 AC XY: 3 AN XY: 673654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000401

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000375

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

Nov 28, 2023

The c.67G>T (p.A23S) alteration is located in exon 1 (coding exon 1) of the ACTR10 gene. This alteration results from a G to T substitution at nucleotide position 67, causing the alanine (A) at amino acid position 23 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	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.79
Sift	Benign	0.037	D
Sift4G	Benign	0.064	T
Polyphen		0.98	D
Vest4		0.25
MutPred		0.79		Gain of ubiquitination at K26 (P = 0.0671);
MVP		0.96
MPC		0.38
ClinPred		0.97	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.70

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: rs1012035360; hg19: chr14-58667002;