22-50092126-C-A

Variant summary

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

The NM_018995.3(MOV10L1):​c.223C>A​(p.Gln75Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,614,136 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q75R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

MOV10L1
NM_018995.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10
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]

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
MOV10L1NM_018995.3 linkuse as main transcriptc.223C>A p.Gln75Lys missense_variant 2/27 ENST00000262794.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MOV10L1ENST00000262794.10 linkuse as main transcriptc.223C>A p.Gln75Lys missense_variant 2/271 NM_018995.3 P1Q9BXT6-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152146
Hom.:
0
Cov.:
32
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:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251484
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135910
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:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000479
AC:
70
AN:
1461872
Hom.:
1
Cov.:
32
AF XY:
0.0000688
AC XY:
50
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000533
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74454
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:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsMay 26, 2024The c.223C>A (p.Q75K) alteration is located in exon 2 (coding exon 2) of the MOV10L1 gene. This alteration results from a C to A substitution at nucleotide position 223, causing the glutamine (Q) at amino acid position 75 to be replaced by a lysine (K). 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
0.29
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T;T;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.90
D;.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.55
D;D;D;D
MetaSVM
Uncertain
0.44
D
MutationAssessor
Pathogenic
3.0
M;M;M;.
MutationTaster
Benign
0.51
D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Uncertain
0.57
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.37
T;T;T;T
Polyphen
0.99
D;D;.;.
Vest4
0.59
MutPred
0.68
Gain of methylation at Q75 (P = 0.0149);Gain of methylation at Q75 (P = 0.0149);Gain of methylation at Q75 (P = 0.0149);.;
MVP
0.92
MPC
0.50
ClinPred
0.48
T
GERP RS
5.2
Varity_R
0.25
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs544105826; hg19: chr22-50530555; API