chrX-74741002-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B.

-17

BP4_StrongBP6_Very_StrongBP7BS2

The NM_001008537.3(NEXMIF):c.3555G>T(p.Gly1185Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,209,561 control chromosomes in the GnomAD database, including 2 homozygotes. There are 94 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., 24 hem., cov: 22)

Exomes 𝑓: 0.00024 ( 2 hom. 70 hem. )

Consequence

NEXMIF
NM_001008537.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0170

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-74741002-C-A is Benign according to our data. Variant chrX-74741002-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 474069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.017 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 24 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 link	c.3555G>T	p.Gly1185Gly	synonymous_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.3555G>T	p.Gly1185Gly	synonymous_variant	Exon 3 of 4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 link	c.3555G>T	p.Gly1185Gly	synonymous_variant	Exon 3 of 5	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 link	c.3555G>T	p.Gly1185Gly	synonymous_variant	Exon 3 of 3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.000753

AC:

AN:

111593

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000475

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0166

Gnomad SAS

AF:

0.000377

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000667

GnomAD2 exomes

AF:

0.00109

AC:

199

AN:

183276

AF XY:

0.000929

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000237

AC:

260

AN:

1097916

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

363300

show subpopulations

African (AFR)

AF:

0.000227

AC:

AN:

26395

American (AMR)

AF:

0.0000284

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00632

AC:

191

AN:

30200

South Asian (SAS)

AF:

0.000111

AC:

AN:

54141

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00000594

AC:

AN:

841850

Other (OTH)

AF:

0.00111

AC:

AN:

46083

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000743

AC:

AN:

111645

Hom.:

Cov.:

AF XY:

0.000709

AC XY:

AN XY:

33855

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

30694

American (AMR)

AF:

0.000475

AC:

AN:

10530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.0164

AC:

AN:

3534

South Asian (SAS)

AF:

0.000378

AC:

AN:

2646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6041

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53136

Other (OTH)

AF:

0.000659

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.000176

Hom.:

Bravo

AF:

0.000722

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 21, 2017

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 21, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.1

(source)

DANN

Benign

0.65

PhyloP100

0.017

Mutation Taster

=100/0

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