1-112689032-C-T

Variant names:

• chr1-112689032-C-T
• rs765144227
• NM_001321324.2:c.235C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321324.2(MOV10):​c.235C>T​(p.Leu79Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. L79V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MOV10 NM_001321324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11918932).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321324.2. 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
	MOV10	NM_001321324.2	MANE Select	c.235C>T	p.Leu79Phe	missense	Exon 3 of 21	NP_001308253.1	Q9HCE1-1
	MOV10	NM_001130079.3		c.235C>T	p.Leu79Phe	missense	Exon 3 of 21	NP_001123551.1	Q9HCE1-1
	MOV10	NM_001369507.1		c.235C>T	p.Leu79Phe	missense	Exon 2 of 20	NP_001356436.1	Q9HCE1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOV10	ENST00000369645.6	TSL:5 MANE Select	c.235C>T	p.Leu79Phe	missense	Exon 3 of 21	ENSP00000358659.1	Q9HCE1-1
	MOV10	ENST00000357443.2	TSL:1	c.235C>T	p.Leu79Phe	missense	Exon 2 of 20	ENSP00000350028.2	Q9HCE1-1
	MOV10	ENST00000413052.6	TSL:1	c.235C>T	p.Leu79Phe	missense	Exon 3 of 21	ENSP00000399797.2	Q9HCE1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251474 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460318 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726466

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4476

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60252

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000225 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0023	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.13
Sift	Benign	0.65	T
Sift4G	Benign	0.73	T
Polyphen		0.63	P
Vest4		0.26
MutPred		0.31		Gain of sheet (P = 0.0827)
MVP		0.65
MPC		0.20
ClinPred		0.13	T
GERP RS		3.3
Varity_R		0.056
gMVP		0.32
Mutation Taster		=96/4	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: rs765144227; hg19: chr1-113231654;