Variant rs757442837 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.3637G>A(p.Gly1213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000081 in 1,210,108 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000086 ( 0 hom. 38 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.212

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=0.05991453).

BP6

Variant X-74740920-C-T is Benign according to our data. Variant chrX-74740920-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 211265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 linkuse as main transcript	c.3637G>A	p.Gly1213Ser	missense_variant	3/4	ENST00000055682.12	NP_001008537.1	Q5QGS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEXMIF	ENST00000055682.12 linkuse as main transcript	c.3637G>A	p.Gly1213Ser	missense_variant	3/4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 linkuse as main transcript	c.3637G>A	p.Gly1213Ser	missense_variant	3/5	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 linkuse as main transcript	c.3637G>A	p.Gly1213Ser	missense_variant	3/3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112040

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34204

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183300

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67814

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 SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000489

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000856

AC:

AN:

1098068

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

363446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000357

AC:

AN:

112040

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 25, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.4

DANN

Benign

0.26

DEOGEN2

Benign

0.046

T;T;.

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.66

.;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

0.49

N;.;.

REVEL

Benign

0.023

Sift

Benign

0.44

T;.;.

Sift4G

Benign

0.75

T;T;.

Polyphen

0.0030

B;B;.

Vest4

0.027

MutPred

0.11

Gain of phosphorylation at G1213 (P = 0.0399);Gain of phosphorylation at G1213 (P = 0.0399);Gain of phosphorylation at G1213 (P = 0.0399);

MVP

0.16

MPC

0.23

ClinPred

0.016

GERP RS

1.2

Varity_R

0.053

gMVP

0.23

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