chr22-50144197-A-G

Variant names:

• chr22-50144197-A-G
• rs2272837
• NM_018995.3:c.2459A>G

Variant summary

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

The NM_018995.3(MOV10L1):​c.2459A>G​(p.Gln820Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,611,384 control chromosomes in the GnomAD database, including 57,359 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5392 hom., cov: 33)
  • Exomes 𝑓: 0.26 (51967 hom.)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 24 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=6.9796693E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOV10L1	NM_018995.3	MANE Select	c.2459A>G	p.Gln820Arg	missense	Exon 18 of 27	NP_061868.1
	MOV10L1	NM_001164104.2		c.2459A>G	p.Gln820Arg	missense	Exon 18 of 26	NP_001157576.1
	MOV10L1	NM_001164105.2		c.2399A>G	p.Gln800Arg	missense	Exon 18 of 26	NP_001157577.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOV10L1	ENST00000262794.10	TSL:1 MANE Select	c.2459A>G	p.Gln820Arg	missense	Exon 18 of 27	ENSP00000262794.5
	MOV10L1	ENST00000395858.7	TSL:1	c.2459A>G	p.Gln820Arg	missense	Exon 18 of 26	ENSP00000379199.3
	MOV10L1	ENST00000540615.5	TSL:2	c.2399A>G	p.Gln800Arg	missense	Exon 18 of 26	ENSP00000438542.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38172 AN: 152060 Hom.: 5377 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.304 AC: 76348 AN: 251142 AF XY: 0.302

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.447

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.575

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.257 AC: 374649 AN: 1459206 Hom.: 51967 Cov.: 33 AF XY: 0.260 AC XY: 188519 AN XY: 725448

African (AFR) AF: 0.210 AC: 7028 AN: 33424

American (AMR) AF: 0.441 AC: 19710 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6621 AN: 26118

East Asian (EAS) AF: 0.569 AC: 22569 AN: 39630

South Asian (SAS) AF: 0.352 AC: 30370 AN: 86214

European-Finnish (FIN) AF: 0.215 AC: 11403 AN: 53122

Middle Eastern (MID) AF: 0.266 AC: 1534 AN: 5758

European-Non Finnish (NFE) AF: 0.233 AC: 259116 AN: 1109962

Other (OTH) AF: 0.270 AC: 16298 AN: 60274

GnomAD4 genome AF: 0.251 AC: 38223 AN: 152178 Hom.: 5392 Cov.: 33 AF XY: 0.254 AC XY: 18890 AN XY: 74414

African (AFR) AF: 0.201 AC: 8361 AN: 41536

American (AMR) AF: 0.359 AC: 5486 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2914 AN: 5170

South Asian (SAS) AF: 0.362 AC: 1747 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2088 AN: 10598

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15842 AN: 67976

Other (OTH) AF: 0.289 AC: 611 AN: 2116

Alfa AF: 0.252 Hom.: 15563

Bravo AF: 0.265

TwinsUK AF: 0.232 AC: 859

ALSPAC AF: 0.230 AC: 887

ESP6500AA AF: 0.193 AC: 851

ESP6500EA AF: 0.240 AC: 2062

ExAC AF: 0.301 AC: 36592

Asia WGS AF: 0.435 AC: 1511 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.98
DANN	Benign	0.36
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.053	T
MetaRNN	Benign	0.0000070	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.87	N
PhyloP100		1.8
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.16
Sift	Benign	0.52	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.096
ClinPred		0.0037	T
GERP RS		-4.2
Varity_R		0.025
gMVP		0.44
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2272837; hg19: chr22-50582626; COSMIC: COSV53168336; COSMIC: COSV53168336;