rs145018752

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001008537.3(NEXMIF):​c.151C>A​(p.Pro51Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,207,568 control chromosomes in the GnomAD database, including 16 homozygotes. There are 389 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P51L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., 187 hem., cov: 23)
Exomes 𝑓: 0.00069 ( 6 hom. 202 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

15

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.730
Variant links:
Genes affected
NEXMIF (HGNC:29433): (neurite extension and migration factor) An inversion on the X chromosome which disrupts this gene and a G-protein coupled purinergic receptor gene located in the pseudoautosomal region of the X chromosome has been linked to X linked cognitive disability.[provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.003943175).
BP6
Variant X-74744406-G-T is Benign according to our data. Variant chrX-74744406-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 129382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00664 (739/111323) while in subpopulation AFR AF = 0.0228 (699/30633). AF 95% confidence interval is 0.0214. There are 10 homozygotes in GnomAd4. There are 187 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEXMIFNM_001008537.3 linkc.151C>A p.Pro51Thr missense_variant Exon 3 of 4 ENST00000055682.12 NP_001008537.1 Q5QGS0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEXMIFENST00000055682.12 linkc.151C>A p.Pro51Thr missense_variant Exon 3 of 4 1 NM_001008537.3 ENSP00000055682.5 Q5QGS0
NEXMIFENST00000616200.2 linkc.151C>A p.Pro51Thr missense_variant Exon 3 of 5 1 ENSP00000480284.1 Q5QGS0
NEXMIFENST00000642681.2 linkc.151C>A p.Pro51Thr missense_variant Exon 3 of 3 ENSP00000495800.1 A0A2R8YEQ5

Frequencies

GnomAD3 genomes
AF:
0.00662
AC:
737
AN:
111270
Hom.:
10
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.0228
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00269
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:
0.00
Gnomad OTH
AF:
0.00805
GnomAD2 exomes
AF:
0.00194
AC:
347
AN:
178482
AF XY:
0.00109
show subpopulations
Gnomad AFR exome
AF:
0.0241
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00113
GnomAD4 exome
AF:
0.000689
AC:
755
AN:
1096245
Hom.:
6
Cov.:
31
AF XY:
0.000558
AC XY:
202
AN XY:
361731
show subpopulations
Gnomad4 AFR exome
AF:
0.0231
AC:
609
AN:
26370
Gnomad4 AMR exome
AF:
0.000996
AC:
35
AN:
35136
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
19367
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
30171
Gnomad4 SAS exome
AF:
0.0000371
AC:
2
AN:
53894
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
40412
Gnomad4 NFE exome
AF:
0.0000357
AC:
30
AN:
840774
Gnomad4 Remaining exome
AF:
0.00159
AC:
73
AN:
46010
Heterozygous variant carriers
0
32
64
95
127
159
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
22
44
66
88
110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00664
AC:
739
AN:
111323
Hom.:
10
Cov.:
23
AF XY:
0.00557
AC XY:
187
AN XY:
33545
show subpopulations
Gnomad4 AFR
AF:
0.0228
AC:
0.0228185
AN:
0.0228185
Gnomad4 AMR
AF:
0.00268
AC:
0.00268199
AN:
0.00268199
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.00
AC:
0
AN:
0
Gnomad4 OTH
AF:
0.00795
AC:
0.00794702
AN:
0.00794702
Heterozygous variant carriers
0
28
56
85
113
141
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00242
Hom.:
106
Bravo
AF:
0.00742
ESP6500AA
AF:
0.0282
AC:
108
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00213
AC:
259

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Sep 25, 2024
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Nov 24, 2014
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:3
Aug 10, 2020
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jan 02, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

X-linked intellectual disability, Cantagrel type Benign:1
Sep 17, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.88
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
2.0
DANN
Benign
0.72
DEOGEN2
Benign
0.020
T;T;.
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.65
.;T;T
MetaRNN
Benign
0.0039
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.62
N;.;.
REVEL
Benign
0.013
Sift
Benign
0.29
T;.;.
Sift4G
Benign
0.69
T;T;.
Polyphen
0.0
B;B;.
Vest4
0.043
MVP
0.043
MPC
0.25
ClinPred
0.0014
T
GERP RS
1.9
Varity_R
0.051
gMVP
0.18
Mutation Taster
=96/4
polymorphism (auto)

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145018752; hg19: chrX-73964241; API