22-50099551-G-T

Variant names:

• chr22-50099551-G-T
• rs140532446
• NM_018995.3:c.391G>T

Variant summary

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

The NM_018995.3(MOV10L1):​c.391G>T​(p.Ala131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A131T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

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

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=0.16991204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOV10L1	NM_018995.3	c.391G>T	p.Ala131Ser	missense_variant	Exon 3 of 27	ENST00000262794.10	NP_061868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOV10L1	ENST00000262794.10	c.391G>T	p.Ala131Ser	missense_variant	Exon 3 of 27	1	NM_018995.3	ENSP00000262794.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

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: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.6
DANN	Benign	0.94
DEOGEN2	Benign	0.052	T;T;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.61	T;.;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M;.
PhyloP100		2.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.84	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.34	T;T;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.14	B;B;.;.
Vest4		0.12
MutPred		0.44		Gain of glycosylation at A131 (P = 0.0043);Gain of glycosylation at A131 (P = 0.0043);Gain of glycosylation at A131 (P = 0.0043);.;
MVP		0.36
MPC		0.092
ClinPred		0.45	T
GERP RS		3.6
Varity_R		0.070
gMVP		0.24
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs140532446; hg19: chr22-50537980;