rs201351157

Positions:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001008537.3(NEXMIF):c.206C>T(p.Ser69Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,209,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 0 hom. 38 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.76

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09154418).

BP6

Variant X-74744351-G-A is Benign according to our data. Variant chrX-74744351-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435604.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXMIF	NM_001008537.3 linkuse as main transcript	c.206C>T	p.Ser69Phe	missense_variant	3/4	ENST00000055682.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NEXMIF	ENST00000055682.12 linkuse as main transcript	c.206C>T	p.Ser69Phe	missense_variant	3/4	1	NM_001008537.3	P1
NEXMIF	ENST00000616200.2 linkuse as main transcript	c.206C>T	p.Ser69Phe	missense_variant	3/5	1		P1
NEXMIF	ENST00000642681.2 linkuse as main transcript	c.206C>T	p.Ser69Phe	missense_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

111677

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33847

show subpopulations

Gnomad AFR

AF:

0.0000977

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:

0.000226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000877

AC:

AN:

182346

Hom.:

AF XY:

0.0000745

AC XY:

AN XY:

67092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

145

AN:

1098002

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

363378

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000134

AC:

AN:

111732

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33912

show subpopulations

Gnomad4 AFR

AF:

0.0000975

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:

0.000226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 17, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 24, 2019	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 20, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.025

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

N;.;.

REVEL

Benign

0.082

Sift

Uncertain

0.0020

D;.;.

Sift4G

Uncertain

0.0040

D;D;.

Polyphen

0.51

P;P;.

Vest4

0.33

MVP

0.20

MPC

0.71

ClinPred

0.18

GERP RS

4.9

Varity_R

0.35

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over