Variant X-74739463-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001008537.3(NEXMIF):c.4493C>A(p.Thr1498Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000376 in 1,197,541 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000040 ( 0 hom. 16 hem. )

Consequence

NEXMIF
NM_001008537.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.40

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.099383056).

BP6

Variant X-74739463-G-T is Benign according to our data. Variant chrX-74739463-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1799619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 linkuse as main transcript	c.4493C>A	p.Thr1498Asn	missense_variant	4/4	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NEXMIF	ENST00000055682.12 linkuse as main transcript	c.4493C>A	p.Thr1498Asn	missense_variant	4/4	1	NM_001008537.3	ENSP00000055682	P1
NEXMIF	ENST00000616200.2 linkuse as main transcript	c.4493C>A	p.Thr1498Asn	missense_variant	4/5	1		ENSP00000480284	P1
NEXMIF	ENST00000642681.2 linkuse as main transcript	c.*633C>A		3_prime_UTR_variant	3/3			ENSP00000495800

Frequencies

GnomAD3 genomes

AF:

0.0000182

AC:

AN:

109722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32016

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:

0.0000379

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000357

AC:

AN:

168121

Hom.:

AF XY:

0.0000721

AC XY:

AN XY:

55481

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000790

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000395

AC:

AN:

1087819

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

354749

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000514

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000182

AC:

AN:

109722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32016

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:

0.0000379

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000494

AC:

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

Ambry Genetics

Jan 26, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.045

T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.51

N;.

REVEL

Benign

0.073

Sift

Uncertain

0.013

D;.

Sift4G

Benign

0.061

T;T

Polyphen

0.51

P;P

Vest4

0.20

MVP

0.11

MPC

0.31

ClinPred

0.12

GERP RS

4.5

Varity_R

0.26

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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