chr22-50090149-G-C

Position:

• chr22-50090149-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018995.3(MOV10L1):​c.61G>C​(p.Glu21Gln) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.388

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2906928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOV10L1	NM_018995.3	c.61G>C	p.Glu21Gln	missense_variant	1/27	ENST00000262794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10L1	ENST00000262794.10	c.61G>C	p.Glu21Gln	missense_variant	1/27	1	NM_018995.3	P1
MOV10L1	ENST00000395858.7	c.61G>C	p.Glu21Gln	missense_variant	1/26	1
MOV10L1	ENST00000395854.6	c.61G>C	p.Glu21Gln	missense_variant, NMD_transcript_variant	1/4	1
MOV10L1	ENST00000419054.5	c.61G>C	p.Glu21Gln	missense_variant, NMD_transcript_variant	1/4	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 15, 2024

The c.61G>C (p.E21Q) alteration is located in exon 1 (coding exon 1) of the MOV10L1 gene. This alteration results from a G to C substitution at nucleotide position 61, causing the glutamic acid (E) at amino acid position 21 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	0.098
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.077	T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.52	T;.;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.031	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		0.038	B;B;.
Vest4		0.050
MutPred		0.10		Gain of MoRF binding (P = 0.1123);Gain of MoRF binding (P = 0.1123);Gain of MoRF binding (P = 0.1123);
MVP		0.88
MPC		0.10
ClinPred		0.14	T
GERP RS		3.7
Varity_R		0.10
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr22-50528578;