1-112694117-A-G

Position:

• chr1-112694117-A-G

Variant summary

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

The NM_001321324.2(MOV10):​c.1240A>G​(p.Lys414Glu) 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. 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: 6.85

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]

(HGNC:):

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=0.3194294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOV10	NM_001321324.2	c.1240A>G	p.Lys414Glu	missense_variant	8/21	ENST00000369645.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10	ENST00000369645.6	c.1240A>G	p.Lys414Glu	missense_variant	8/21	5	NM_001321324.2	P1
	ENST00000421943.1	n.287-267T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

May 06, 2022

The c.1240A>G (p.K414E) alteration is located in exon 8 (coding exon 7) of the MOV10 gene. This alteration results from a A to G substitution at nucleotide position 1240, causing the lysine (K) at amino acid position 414 to be replaced by a glutamic acid (E). 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	0.40
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;T;T
Eigen	Benign	0.055
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	.;.;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.99	L;L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Pathogenic	0.72
Sift	Benign	0.066	T;T;T;T
Sift4G	Benign	0.066	T;T;T;T
Polyphen		0.11	B;B;B;B
Vest4		0.45
MutPred		0.39		Loss of ubiquitination at K414 (P = 0.0103);Loss of ubiquitination at K414 (P = 0.0103);.;Loss of ubiquitination at K414 (P = 0.0103);
MVP		0.95
MPC		0.91
ClinPred		0.82	D
GERP RS		4.9
Varity_R		0.15
gMVP		0.76

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: chr1-113236739;