Genetic Variant NEXMIF:p.Asp1487Asn (chrX-74739497-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008537.3(NEXMIF):c.4459G>A(p.Asp1487Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1487G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 21)

Consequence

NEXMIF
NM_001008537.3 missense, splice_region

Scores

Splicing: ADA: 0.004636

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

Publications

0 publications found

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]

NEXMIF Gene-Disease associations (from GenCC):

X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
X-linked intellectual disability, Cantagrel type
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
myoclonic-astatic epilepsy
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

NEXMIF links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21202248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008537.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEXMIF	NM_001008537.3	MANE Select	c.4459G>A	p.Asp1487Asn	missense splice_region	Exon 4 of 4	NP_001008537.1	Q5QGS0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEXMIF	ENST00000055682.12	TSL:1 MANE Select	c.4459G>A	p.Asp1487Asn	missense splice_region	Exon 4 of 4	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2	TSL:1	c.4459G>A	p.Asp1487Asn	missense splice_region	Exon 4 of 5	ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2		c.*599G>A		3_prime_UTR	Exon 3 of 3	ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.89

PhyloP100

4.3

PrimateAI

Benign

0.41

PROVEAN

Benign

0.16

REVEL

Benign

0.072

Sift

Benign

0.036

Sift4G

Uncertain

0.037

Polyphen

0.45

Vest4

0.23

MutPred

0.35

Gain of methylation at K1484 (P = 0.0805)

MVP

0.35

MPC

0.22

ClinPred

0.46

GERP RS

5.3

Varity_R

0.15

gMVP

0.13

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0046

dbscSNV1_RF

Benign

0.11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over