chr22-50099582-C-G

Position:

• chr22-50099582-C-G

Variant summary

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

The NM_018995.3(MOV10L1):​c.422C>G​(p.Ser141Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.32

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 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	c.422C>G	p.Ser141Cys	missense_variant	3/27	ENST00000262794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOV10L1	ENST00000262794.10	c.422C>G	p.Ser141Cys	missense_variant	3/27	1	NM_018995.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

Aug 04, 2023

The c.422C>G (p.S141C) alteration is located in exon 3 (coding exon 3) of the MOV10L1 gene. This alteration results from a C to G substitution at nucleotide position 422, causing the serine (S) at amino acid position 141 to be replaced by a cysteine (C). 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	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;.;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T;.;T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	2.9	M;M;M;.
MutationTaster	Benign	0.58	D;D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.015	D;D;D;D
Sift4G	Uncertain	0.041	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.50
MutPred		0.52		Gain of catalytic residue at L142 (P = 0.0112);Gain of catalytic residue at L142 (P = 0.0112);Gain of catalytic residue at L142 (P = 0.0112);.;
MVP		0.75
MPC		0.36
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs781497595; hg19: chr22-50538011;