chr22-50108237-C-T

Variant names:

• chr22-50108237-C-T
• rs3810971
• NM_018995.3:c.544C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The NM_018995.3(MOV10L1):​c.544C>T​(p.Arg182Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,612,090 control chromosomes in the GnomAD database, including 48,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4207 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44042 hom.)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.70
• Publications: 27 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 -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 22-50108237-C-T is Benign according to our data. Variant chr22-50108237-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOV10L1	NM_018995.3	MANE Select	c.544C>T	p.Arg182Cys	missense	Exon 4 of 27	NP_061868.1	Q9BXT6-1
	MOV10L1	NM_001164104.2		c.544C>T	p.Arg182Cys	missense	Exon 4 of 26	NP_001157576.1	Q9BXT6-4
	MOV10L1	NM_001164105.2		c.484C>T	p.Arg162Cys	missense	Exon 4 of 26	NP_001157577.1	Q9BXT6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOV10L1	ENST00000262794.10	TSL:1 MANE Select	c.544C>T	p.Arg182Cys	missense	Exon 4 of 27	ENSP00000262794.5	Q9BXT6-1
	MOV10L1	ENST00000395858.7	TSL:1	c.544C>T	p.Arg182Cys	missense	Exon 4 of 26	ENSP00000379199.3	Q9BXT6-4
	MOV10L1	ENST00000395854.6	TSL:1	n.*700C>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000379195.2	F2Z2H1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34121 AN: 152000 Hom.: 4193 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.264

GnomAD2 exomes AF: 0.266 AC: 65929 AN: 248206 AF XY: 0.266

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.247

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.202

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.242 AC: 353395 AN: 1459972 Hom.: 44042 Cov.: 34 AF XY: 0.244 AC XY: 177415 AN XY: 726202

African (AFR) AF: 0.158 AC: 5285 AN: 33468

American (AMR) AF: 0.407 AC: 18102 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6285 AN: 26124

East Asian (EAS) AF: 0.281 AC: 11129 AN: 39650

South Asian (SAS) AF: 0.315 AC: 27092 AN: 86010

European-Finnish (FIN) AF: 0.203 AC: 10826 AN: 53286

Middle Eastern (MID) AF: 0.254 AC: 1462 AN: 5756

European-Non Finnish (NFE) AF: 0.233 AC: 258450 AN: 1110904

Other (OTH) AF: 0.245 AC: 14764 AN: 60322

GnomAD4 genome AF: 0.225 AC: 34164 AN: 152118 Hom.: 4207 Cov.: 32 AF XY: 0.226 AC XY: 16790 AN XY: 74352

African (AFR) AF: 0.155 AC: 6430 AN: 41510

American (AMR) AF: 0.352 AC: 5383 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3472

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5162

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4822

European-Finnish (FIN) AF: 0.188 AC: 1993 AN: 10586

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15727 AN: 67970

Other (OTH) AF: 0.271 AC: 572 AN: 2110

Alfa AF: 0.234 Hom.: 14414

Bravo AF: 0.235

TwinsUK AF: 0.240 AC: 891

ALSPAC AF: 0.239 AC: 921

ESP6500AA AF: 0.151 AC: 665

ESP6500EA AF: 0.239 AC: 2052

ExAC AF: 0.262 AC: 31758

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.22
MPC		0.52
ClinPred		0.030	T
GERP RS		4.2
Varity_R		0.61
gMVP		0.46
Mutation Taster		=278/22	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.53		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.53		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3810971; hg19: chr22-50546666; COSMIC: COSV53168698; COSMIC: COSV53168698;