14-58202887-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018477.3(ACTR10):​c.110G>T​(p.Cys37Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C37Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ACTR10 NM_018477.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36148173).

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.110G>T	p.Cys37Phe	missense	Exon 2 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.110G>T	p.Cys37Phe	missense	Exon 2 of 13	ENSP00000254286.4	Q9NZ32
	ACTR10	ENST00000554402.6	TSL:1	n.107G>T		non_coding_transcript_exon	Exon 2 of 14	ENSP00000477173.1	V9GYX7
	ACTR10	ENST00000852594.1		c.137G>T	p.Cys46Phe	missense	Exon 2 of 13	ENSP00000522653.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456136 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724394

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 44082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.00 AC: 0 AN: 85084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109250

Other (OTH) AF: 0.00 AC: 0 AN: 60124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.18	N
PhyloP100		7.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.32
Sift	Benign	0.72	T
Sift4G	Benign	0.75	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.37		Loss of sheet (P = 0.0817)
MVP		0.94
MPC		0.46
ClinPred		0.77	D
GERP RS		5.6
Varity_R		0.34
gMVP		0.79
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1320026758; hg19: chr14-58669605;