22-50099473-G-A

Variant names:

• chr22-50099473-G-A
• rs762299641
• NM_018995.3:c.313G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018995.3(MOV10L1):​c.313G>A​(p.Asp105Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000836 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000085 (0 hom.)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035629183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOV10L1	NM_018995.3	c.313G>A	p.Asp105Asn	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.313G>A	p.Asp105Asn	missense_variant	Exon 3 of 27	1	NM_018995.3	ENSP00000262794.5

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251328 AF XY: 0.0000515

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000848 AC: 124 AN: 1461832 Hom.: 0 Cov.: 30 AF XY: 0.0000880 AC XY: 64 AN XY: 727208

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000953 AC: 106 AN: 1111986

Other (OTH) AF: 0.000149 AC: 9 AN: 60392

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313G>A (p.D105N) alteration is located in exon 3 (coding exon 3) of the MOV10L1 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the aspartic acid (D) at amino acid position 105 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.48
DEOGEN2	Benign	0.060	T;T;.;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	T;.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.036	T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M;M;M;.
PhyloP100		1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.67	T;T;T;T
Sift4G	Benign	0.82	T;T;T;T
Polyphen		0.0030	B;B;.;.
Vest4		0.16
MutPred		0.41		Loss of phosphorylation at S106 (P = 0.1354);Loss of phosphorylation at S106 (P = 0.1354);Loss of phosphorylation at S106 (P = 0.1354);.;
MVP		0.58
MPC		0.088
ClinPred		0.029	T
GERP RS		2.5
Varity_R		0.032
gMVP		0.29
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs762299641; hg19: chr22-50537902; COSMIC: COSV99433434; COSMIC: COSV99433434;