chr1-112674995-T-G

Position:

• chr1-112674995-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001321324.2(MOV10):​c.83T>G​(p.Met28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: MOV10 NM_001321324.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.695

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, MOV10
• BP4: Computational evidence support a benign effect (MetaRNN=0.042746216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOV10	NM_001321324.2	c.83T>G	p.Met28Arg	missense_variant	2/21	ENST00000369645.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10	ENST00000369645.6	c.83T>G	p.Met28Arg	missense_variant	2/21	5	NM_001321324.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 11, 2024

The c.83T>G (p.M28R) alteration is located in exon 2 (coding exon 1) of the MOV10 gene. This alteration results from a T to G substitution at nucleotide position 83, causing the methionine (M) at amino acid position 28 to be replaced by an arginine (R). 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	0.060
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.77
DEOGEN2	Benign	0.25	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.43	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.54	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.090
MutPred		0.21		Gain of phosphorylation at T30 (P = 0.0414);Gain of phosphorylation at T30 (P = 0.0414);Gain of phosphorylation at T30 (P = 0.0414);
MVP		0.47
MPC		1.7
ClinPred		0.038	T
GERP RS		-4.3
Varity_R		0.48
gMVP		0.34

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: chr1-113217617;