Variant chr22-50108136-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018995.3(MOV10L1):c.443G>C(p.Gly148Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000682 in 1,613,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MOV10L1
NM_018995.3 missense, splice_region

Scores

Splicing: ADA: 0.04594

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

Variant links:

Genes affected

MOV10L1 (HGNC:7201): (Mov10 like RNA helicase 1) This gene is similar to a mouse gene that encodes a putative RNA helicase and shows testis-specific expression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

MOV10L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
MOV10L1	NM_018995.3 linkuse as main transcript	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	4/27	ENST00000262794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10L1	ENST00000262794.10 linkuse as main transcript	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	4/27	1	NM_018995.3	P1	Q9BXT6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250604

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135598

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461152

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.443G>C (p.G148A) alteration is located in exon 4 (coding exon 4) of the MOV10L1 gene. This alteration results from a G to C substitution at nucleotide position 443, causing the glycine (G) at amino acid position 148 to be replaced by an alanine (A). 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

0.48

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.21

T;T;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;.;T;T

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.097

T;T;T;T

Sift4G

Benign

0.079

T;T;T;T

Polyphen

0.69

P;P;.;.

Vest4

0.66

MutPred

0.56

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;

MVP

0.70

MPC

0.17

ClinPred

0.31

GERP RS

3.1

Varity_R

0.27

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.046

dbscSNV1_RF

Benign

0.45

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over