chr1-112689859-T-A

Position:

• chr1-112689859-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321324.2(MOV10):​c.597T>A​(p.His199Gln) 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. 16/21 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: -0.664

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051570863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOV10	NM_001321324.2	c.597T>A	p.His199Gln	missense_variant	5/21	ENST00000369645.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10	ENST00000369645.6	c.597T>A	p.His199Gln	missense_variant	5/21	5	NM_001321324.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 09, 2023

The c.597T>A (p.H199Q) alteration is located in exon 5 (coding exon 4) of the MOV10 gene. This alteration results from a T to A substitution at nucleotide position 597, causing the histidine (H) at amino acid position 199 to be replaced by a glutamine (Q). 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	0.092
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.010
DANN	Benign	0.77
DEOGEN2	Benign	0.25	T;T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.53	.;.;T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.78	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.55	T;T;T;T
Sift4G	Benign	0.57	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.19
MutPred		0.42		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;Gain of sheet (P = 0.0221);
MVP		0.39
MPC		0.19
ClinPred		0.031	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.55

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: chr1-113232481;