rs894871556

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008537.3(NEXMIF):​c.2363T>G​(p.Leu788Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000893 in 112,044 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Consequence

NEXMIF
NM_001008537.3 missense

Scores

1
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17
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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18056571).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEXMIFNM_001008537.3 linkc.2363T>G p.Leu788Arg 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.2363T>G p.Leu788Arg missense_variant Exon 3 of 4 1 NM_001008537.3 ENSP00000055682.5 Q5QGS0
NEXMIFENST00000616200.2 linkc.2363T>G p.Leu788Arg missense_variant Exon 3 of 5 1 ENSP00000480284.1 Q5QGS0
NEXMIFENST00000642681.2 linkc.2363T>G p.Leu788Arg missense_variant Exon 3 of 3 ENSP00000495800.1 A0A2R8YEQ5

Frequencies

GnomAD3 genomes
AF:
0.00000893
AC:
1
AN:
112044
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34194
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000893
AC:
1
AN:
112044
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34194
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Dec 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 788 of the NEXMIF protein (p.Leu788Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEXMIF-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T;.
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.78
.;T;T
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.72
N;.;.
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D;.;.
Sift4G
Uncertain
0.022
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.60
MutPred
0.22
Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);
MVP
0.51
MPC
1.0
ClinPred
0.96
D
GERP RS
3.3
Varity_R
0.53
gMVP
0.54

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: rs894871556; hg19: chrX-73962029; API