rs145018752

Positions:

chrX-74744406-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001008537.3(NEXMIF):c.151C>A(p.Pro51Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,207,568 control chromosomes in the GnomAD database, including 16 homozygotes. There are 389 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., 187 hem., cov: 23)

Exomes 𝑓: 0.00069 ( 6 hom. 202 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.730

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003943175).

BP6

Variant X-74744406-G-T is Benign according to our data. Variant chrX-74744406-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 129382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00664 (739/111323) while in subpopulation AFR AF= 0.0228 (699/30633). AF 95% confidence interval is 0.0214. There are 10 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 linkuse as main transcript	c.151C>A	p.Pro51Thr	missense_variant	3/4	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NEXMIF	ENST00000055682.12 linkuse as main transcript	c.151C>A	p.Pro51Thr	missense_variant	3/4	1	NM_001008537.3	ENSP00000055682	P1
NEXMIF	ENST00000616200.2 linkuse as main transcript	c.151C>A	p.Pro51Thr	missense_variant	3/5	1		ENSP00000480284	P1
NEXMIF	ENST00000642681.2 linkuse as main transcript	c.151C>A	p.Pro51Thr	missense_variant	3/3			ENSP00000495800

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

737

AN:

111270

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

185

AN XY:

33482

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

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:

0.00

Gnomad OTH

AF:

0.00805

GnomAD3 exomes

AF:

0.00194

AC:

347

AN:

178482

Hom.:

AF XY:

0.00109

AC XY:

AN XY:

64152

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000538

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000689

AC:

755

AN:

1096245

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

202

AN XY:

361731

show subpopulations

Gnomad4 AFR exome

AF:

0.0231

Gnomad4 AMR exome

AF:

0.000996

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000357

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00664

AC:

739

AN:

111323

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

187

AN XY:

33545

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00795

Alfa

AF:

0.000782

Hom.:

Bravo

AF:

0.00742

ESP6500AA

AF:

0.0282

AC:

108

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00213

AC:

259

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 20, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 24, 2014	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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.0

DANN

Benign

0.72

DEOGEN2

Benign

0.020

T;T;.

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.65

.;T;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.62

N;.;.

REVEL

Benign

0.013

Sift

Benign

0.29

T;.;.

Sift4G

Benign

0.69

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.043

MVP

0.043

MPC

0.25

ClinPred

0.0014

GERP RS

1.9

Varity_R

0.051

gMVP

0.18

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