rs41306133

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001008537.3(NEXMIF):c.2801A>G(p.Asn934Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,209,520 control chromosomes in the GnomAD database, including 95 homozygotes. There are 5,511 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 7 hom., 360 hem., cov: 23)

Exomes 𝑓: 0.015 ( 88 hom. 5151 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.181

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036647618).

BP6

Variant X-74741756-T-C is Benign according to our data. Variant chrX-74741756-T-C is described in ClinVar as Benign. ClinVar VariationId is 474066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0147 (16130/1097650) while in subpopulation NFE AF = 0.0165 (13860/841604). AF 95% confidence interval is 0.0162. There are 88 homozygotes in GnomAdExome4. There are 5151 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 link	c.2801A>G	p.Asn934Ser	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.2801A>G	p.Asn934Ser	missense_variant	Exon 3 of 4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 link	c.2801A>G	p.Asn934Ser	missense_variant	Exon 3 of 5	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 link	c.2801A>G	p.Asn934Ser	missense_variant	Exon 3 of 3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1169

AN:

111819

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00291

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.00227

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00409

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.00470

GnomAD2 exomes

AF:

0.0119

AC:

2184

AN:

183274

AF XY:

0.0120

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00441

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0147

AC:

16130

AN:

1097650

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

5151

AN XY:

363038

show subpopulations

African (AFR)

AF:

0.00148

AC:

AN:

26392

American (AMR)

AF:

0.0111

AC:

392

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00562

AC:

109

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00617

AC:

334

AN:

54132

European-Finnish (FIN)

AF:

0.0199

AC:

808

AN:

40530

Middle Eastern (MID)

AF:

0.00387

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0165

AC:

13860

AN:

841604

Other (OTH)

AF:

0.0124

AC:

572

AN:

46070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

654

1307

1961

2614

3268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0105

AC:

1177

AN:

111870

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

360

AN XY:

34076

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

30827

American (AMR)

AF:

0.0158

AC:

167

AN:

10548

Ashkenazi Jewish (ASJ)

AF:

0.00227

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3540

South Asian (SAS)

AF:

0.00410

AC:

AN:

2684

European-Finnish (FIN)

AF:

0.0181

AC:

110

AN:

6094

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0152

AC:

810

AN:

53121

Other (OTH)

AF:

0.00464

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0139

Hom.:

683

Bravo

AF:

0.00942

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0173

AC:

ESP6500AA

AF:

0.00339

AC:

ESP6500EA

AF:

0.0153

AC:

103

ExAC

AF:

0.0117

AC:

1416

EpiCase

AF:

0.0150

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 16, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 31, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 13, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.016

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.019

T;T;.

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.67

.;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-0.97

PhyloP100

0.18

PrimateAI

Benign

0.27

PROVEAN

Benign

0.67

N;.;.

REVEL

Benign

0.10

Sift

Benign

1.0

T;.;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.035

MPC

0.18

ClinPred

0.0027

GERP RS

-7.2

Varity_R

0.033

gMVP

0.058

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over