rs199960807

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001008537.3(NEXMIF):c.133G>A(p.Ala45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000759 in 1,205,848 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 259 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 0.00031 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00080 ( 0 hom. 251 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 0.496

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013754636).

BP6

Variant X-74744424-C-T is Benign according to our data. Variant chrX-74744424-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 289284.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=3, Uncertain_significance=2}. Variant chrX-74744424-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 3 of 4	ENST00000055682.12	NP_001008537.1	Q5QGS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEXMIF	ENST00000055682.12 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 3 of 4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 3 of 5	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 link	c.133G>A	p.Ala45Thr	missense_variant	Exon 3 of 3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

111220

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

AN XY:

33408

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000383

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000671

GnomAD3 exomes

AF:

0.000284

AC:

AN:

176128

Hom.:

AF XY:

0.000241

AC XY:

AN XY:

62152

show subpopulations

Gnomad AFR exome

AF:

0.0000776

Gnomad AMR exome

AF:

0.0000745

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000556

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000804

AC:

880

AN:

1094574

Hom.:

Cov.:

AF XY:

0.000697

AC XY:

251

AN XY:

360152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000574

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000298

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000993

Gnomad4 OTH exome

AF:

0.000588

GnomAD4 genome

AF:

0.000315

AC:

AN:

111274

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

AN XY:

33472

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000384

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.000424

Hom.:

Bravo

AF:

0.000302

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Mar 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NEXMIF: BP4, BS2 -

Jul 19, 2016

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1Benign:1

Jul 09, 2017

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. -

Apr 15, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.021

T;T;.

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.65

.;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.21

N;.;.

REVEL

Benign

0.085

Sift

Benign

0.77

T;.;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0010

B;B;.

Vest4

0.069

MVP

0.043

MPC

0.22

ClinPred

0.0059

GERP RS

1.2

Varity_R

0.043

gMVP

0.15

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