22-50108204-G-A

Position:

• chr22-50108204-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_018995.3(MOV10L1):​c.511G>A​(p.Glu171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,614,070 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (3 hom.)
• Consequence: MOV10L1 NM_018995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

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]

MOV10L1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04287961).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000456 (667/1461806) while in subpopulation MID AF= 0.0184 (106/5768). AF 95% confidence interval is 0.0155. There are 3 homozygotes in gnomad4_exome. There are 329 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOV10L1	NM_018995.3	c.511G>A	p.Glu171Lys	missense_variant	4/27	ENST00000262794.10	NP_061868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOV10L1	ENST00000262794.10	c.511G>A	p.Glu171Lys	missense_variant	4/27	1	NM_018995.3	ENSP00000262794.5

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000475 AC: 119 AN: 250604 Hom.: 0 AF XY: 0.000516 AC XY: 70 AN XY: 135678

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000663

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000456 AC: 667 AN: 1461806 Hom.: 3 Cov.: 31 AF XY: 0.000452 AC XY: 329 AN XY: 727202

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.000804

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.000487

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.000696

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74446

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000527 Hom.: 0

Bravo AF: 0.000348

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000593 AC: 72

EpiCase AF: 0.000818

EpiControl AF: 0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.511G>A (p.E171K) alteration is located in exon 4 (coding exon 4) of the MOV10L1 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the glutamic acid (E) at amino acid position 171 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T;T;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.82	T;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.043	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.34	T;T;T;T
Sift4G	Benign	0.63	T;T;T;T
Polyphen		0.21	B;B;.;.
Vest4		0.38
MVP		0.42
MPC		0.11
ClinPred		0.038	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs147590689; hg19: chr22-50546633; COSMIC: COSV53175580; COSMIC: COSV53175580;