22-50092126-C-T

Variant names:

• chr22-50092126-C-T
• rs544105826
• NM_018995.3:c.223C>T

Variant summary

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

The NM_018995.3(MOV10L1):​c.223C>T​(p.Gln75*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MOV10L1 NM_018995.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.223C>T	p.Gln75*	stop_gained	Exon 2 of 27	NP_061868.1	Q9BXT6-1
	MOV10L1	NM_001164104.2		c.223C>T	p.Gln75*	stop_gained	Exon 2 of 26	NP_001157576.1	Q9BXT6-4
	MOV10L1	NM_001164105.2		c.163C>T	p.Gln55*	stop_gained	Exon 2 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.223C>T	p.Gln75*	stop_gained	Exon 2 of 27	ENSP00000262794.5	Q9BXT6-1
	MOV10L1	ENST00000395858.7	TSL:1	c.223C>T	p.Gln75*	stop_gained	Exon 2 of 26	ENSP00000379199.3	Q9BXT6-4
	MOV10L1	ENST00000395854.6	TSL:1	n.*379C>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000379195.2	F2Z2H1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727236

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: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Benign	0.75	D
PhyloP100		5.1
Vest4		0.47
GERP RS		5.2
Mutation Taster		=27/173	disease causing (fs/PTC)

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: rs544105826; hg19: chr22-50530555;