rs201351157

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 13/20 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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 435604. Variant chrX-74744351-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 435604. Variant chrX-74744351-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 435604. Variant chrX-74744351-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 435604.

BS2

High Hemizygotes in GnomAd4 at 2 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 link	c.206C>T	p.Ser69Phe	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.206C>T	p.Ser69Phe	missense_variant	Exon 3 of 4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 link	c.206C>T	p.Ser69Phe	missense_variant	Exon 3 of 5	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 link	c.206C>T	p.Ser69Phe	missense_variant	Exon 3 of 3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

111677

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000877

AC:

AN:

182346

AF XY:

0.0000745

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 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

African (AFR)

AF:

0.00

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35199

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.00

AC:

AN:

54131

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40507

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4123

European-Non Finnish (NFE)

AF:

0.000169

AC:

142

AN:

841980

Other (OTH)

AF:

0.0000434

AC:

AN:

46079

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000134

AC:

AN:

111732

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33912

show subpopulations

African (AFR)

AF:

0.0000975

AC:

AN:

30768

American (AMR)

AF:

0.00

AC:

AN:

10494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3534

South Asian (SAS)

AF:

0.00

AC:

AN:

2639

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6073

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

53155

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.0000868

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

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 24, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function -

not specified

Uncertain:1

Oct 20, 2015

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

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-0.93

PhyloP100

2.8

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

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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