rs9617066

Variant names:

• chr22-50092072-A-T
• rs9617066
• NM_018995.3:c.169A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018995.3(MOV10L1):​c.169A>T​(p.Met57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,814 control chromosomes in the GnomAD database, including 48,359 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. M57T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.23 (4225 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44134 hom.)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002233982).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOV10L1	NM_018995.3	c.169A>T	p.Met57Leu	missense_variant	Exon 2 of 27	ENST00000262794.10	NP_061868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOV10L1	ENST00000262794.10	c.169A>T	p.Met57Leu	missense_variant	Exon 2 of 27	1	NM_018995.3	ENSP00000262794.5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34319 AN: 152016 Hom.: 4210 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.266 AC: 66890 AN: 251428 AF XY: 0.266

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.407

Gnomad ASJ exome AF: 0.247

Gnomad EAS exome AF: 0.275

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.242 AC: 353974 AN: 1461680 Hom.: 44134 Cov.: 34 AF XY: 0.244 AC XY: 177709 AN XY: 727156

African (AFR) AF: 0.166 AC: 5553 AN: 33474

American (AMR) AF: 0.405 AC: 18125 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6287 AN: 26136

East Asian (EAS) AF: 0.282 AC: 11187 AN: 39686

South Asian (SAS) AF: 0.315 AC: 27204 AN: 86248

European-Finnish (FIN) AF: 0.203 AC: 10847 AN: 53414

Middle Eastern (MID) AF: 0.255 AC: 1470 AN: 5768

European-Non Finnish (NFE) AF: 0.233 AC: 258508 AN: 1111846

Other (OTH) AF: 0.245 AC: 14793 AN: 60392

GnomAD4 genome AF: 0.226 AC: 34364 AN: 152134 Hom.: 4225 Cov.: 32 AF XY: 0.227 AC XY: 16911 AN XY: 74396

African (AFR) AF: 0.161 AC: 6678 AN: 41522

American (AMR) AF: 0.351 AC: 5366 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5170

South Asian (SAS) AF: 0.315 AC: 1519 AN: 4816

European-Finnish (FIN) AF: 0.188 AC: 1985 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15694 AN: 67976

Other (OTH) AF: 0.272 AC: 574 AN: 2112

Alfa AF: 0.227 Hom.: 1356

Bravo AF: 0.236

TwinsUK AF: 0.241 AC: 893

ALSPAC AF: 0.238 AC: 918

ESP6500AA AF: 0.159 AC: 699

ESP6500EA AF: 0.238 AC: 2048

ExAC AF: 0.264 AC: 31990

Asia WGS AF: 0.301 AC: 1044 AN: 3478

EpiCase AF: 0.226

EpiControl AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.5
DANN	Benign	0.61
DEOGEN2	Benign	0.040	T;T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.0084	T;.;T;T
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.2	N;N;N;.
PhyloP100		-1.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.54	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.054
MutPred		0.20		Gain of catalytic residue at M57 (P = 0.0051);Gain of catalytic residue at M57 (P = 0.0051);Gain of catalytic residue at M57 (P = 0.0051);.;
MPC		0.082
ClinPred		0.0012	T
GERP RS		-0.97
Varity_R		0.053
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs9617066; hg19: chr22-50530501; COSMIC: COSV53168683; COSMIC: COSV53168683;