1-112689441-G-A

Position:

• chr1-112689441-G-A

Variant summary

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

The NM_001321324.2(MOV10):​c.368G>A​(p.Gly123Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOV10 NM_001321324.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.01

Genes affected

MOV10 (HGNC:7200): (Mov10 RNA helicase) Enables 5'-3' RNA helicase activity and RNA binding activity. Involved in defense response to virus; negative regulation of transposition, RNA-mediated; and posttranscriptional regulation of gene expression. Located in P-body and cytosol. Implicated in hypertension. [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	UniProt
MOV10	NM_001321324.2	c.368G>A	p.Gly123Asp	missense_variant	4/21	ENST00000369645.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10	ENST00000369645.6	c.368G>A	p.Gly123Asp	missense_variant	4/21	5	NM_001321324.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jun 10, 2022

The c.368G>A (p.G123D) alteration is located in exon 4 (coding exon 3) of the MOV10 gene. This alteration results from a G to A substitution at nucleotide position 368, causing the glycine (G) at amino acid position 123 to be replaced by an aspartic acid (D). 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	0.42
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	.;.;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.1	M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.91	P;P;P;P
Vest4		0.68
MutPred		0.51		Gain of catalytic residue at G123 (P = 0.0118);Gain of catalytic residue at G123 (P = 0.0118);.;Gain of catalytic residue at G123 (P = 0.0118);
MVP		0.85
MPC		0.52
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.49
gMVP		0.87

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: chr1-113232063;