X-74739478-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001008537.3(NEXMIF):​c.4478T>G​(p.Leu1493Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 21)

Consequence

NEXMIF
NM_001008537.3 missense

Scores

4
5
7

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.89
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXMIFNM_001008537.3 linkuse as main transcriptc.4478T>G p.Leu1493Arg missense_variant 4/4 ENST00000055682.12 NP_001008537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEXMIFENST00000055682.12 linkuse as main transcriptc.4478T>G p.Leu1493Arg missense_variant 4/41 NM_001008537.3 ENSP00000055682 P1
NEXMIFENST00000616200.2 linkuse as main transcriptc.4478T>G p.Leu1493Arg missense_variant 4/51 ENSP00000480284 P1
NEXMIFENST00000642681.2 linkuse as main transcriptc.*618T>G 3_prime_UTR_variant 3/3 ENSP00000495800

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
21

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NEXMIF-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 22, 2024The NEXMIF c.4478T>G variant is predicted to result in the amino acid substitution p.Leu1493Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.088
T;T
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.71
.;T
M_CAP
Pathogenic
0.41
D
MetaRNN
Pathogenic
0.80
D;D
MetaSVM
Benign
-0.79
T
MutationTaster
Benign
0.85
D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.4
N;.
REVEL
Benign
0.18
Sift
Uncertain
0.0020
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.74
MutPred
0.33
Gain of disorder (P = 0.0432);Gain of disorder (P = 0.0432);
MVP
0.61
MPC
0.96
ClinPred
0.68
D
GERP RS
5.5
Varity_R
0.65
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-73959313; API