14-58232123-T-A

Position:

• chr14-58232123-T-A

Variant summary

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

The NM_018477.3(ACTR10):​c.928T>A​(p.Ser310Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTR10 NM_018477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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=0.39890444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR10	NM_018477.3	c.928T>A	p.Ser310Thr	missense_variant	12/13	ENST00000254286.9
ACTR10	XM_011536960.2	c.949T>A	p.Ser317Thr	missense_variant	12/13
ACTR10	XM_011536961.2	c.892T>A	p.Ser298Thr	missense_variant	11/12
ACTR10	XM_047431587.1	c.355T>A	p.Ser119Thr	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR10	ENST00000254286.9	c.928T>A	p.Ser310Thr	missense_variant	12/13	1	NM_018477.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 11, 2023

The c.928T>A (p.S310T) alteration is located in exon 12 (coding exon 12) of the ACTR10 gene. This alteration results from a T to A substitution at nucleotide position 928, causing the serine (S) at amino acid position 310 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.53	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.060	N
REVEL	Uncertain	0.29
Sift	Benign	0.68	T
Sift4G	Benign	0.81	T
Polyphen		0.0080	B
Vest4		0.42
MutPred		0.63		Gain of helix (P = 0.1736);
MVP		0.92
MPC		0.32
ClinPred		0.74	D
GERP RS		4.6
Varity_R		0.079
gMVP		0.77

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: rs1252970519; hg19: chr14-58698841;