Variant rs61741844 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001008537.3(NEXMIF):c.1132A>G(p.Lys378Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,209,594 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K378Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.000024 ( 0 hom. 13 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.77

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017428815).

BP6

Variant X-74743425-T-C is Benign according to our data. Variant chrX-74743425-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXMIF	NM_001008537.3 linkuse as main transcript	c.1132A>G	p.Lys378Glu	missense_variant	3/4	ENST00000055682.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NEXMIF	ENST00000055682.12 linkuse as main transcript	c.1132A>G	p.Lys378Glu	missense_variant	3/4	1	NM_001008537.3	P1
NEXMIF	ENST00000616200.2 linkuse as main transcript	c.1132A>G	p.Lys378Glu	missense_variant	3/5	1		P1
NEXMIF	ENST00000642681.2 linkuse as main transcript	c.1132A>G	p.Lys378Glu	missense_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.000215

AC:

AN:

111469

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33645

show subpopulations

Gnomad AFR

AF:

0.000687

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000955

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000656

AC:

AN:

183005

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

67565

show subpopulations

Gnomad AFR exome

AF:

0.000837

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1098070

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

363432

show subpopulations

Gnomad4 AFR exome

AF:

0.000833

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000224

AC:

AN:

111524

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33710

show subpopulations

Gnomad4 AFR

AF:

0.000718

Gnomad4 AMR

AF:

0.0000953

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000227

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 02, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T;.

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.61

.;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.21

N;.;.

REVEL

Benign

0.039

Sift

Benign

0.22

T;.;.

Sift4G

Benign

0.62

T;T;.

Polyphen

0.0080

B;B;.

Vest4

0.16

MVP

0.17

MPC

0.32

ClinPred

0.018

GERP RS

4.3

Varity_R

0.18

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