Variant X-74739447-A-G 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.4509T>C(p.Pro1503=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00105 in 1,198,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 372 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 0.00052 ( 0 hom., 10 hem., cov: 21)

Exomes 𝑓: 0.0011 ( 0 hom. 362 hem. )

Consequence

NEXMIF
NM_001008537.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.42

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 (BayesDel_noAF=-0.54).

BP6

Variant X-74739447-A-G is Benign according to our data. Variant chrX-74739447-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 211270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 linkuse as main transcript	c.4509T>C	p.Pro1503=	synonymous_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.4509T>C	p.Pro1503=	synonymous_variant	4/4	1	NM_001008537.3	ENSP00000055682	P1
NEXMIF	ENST00000616200.2 linkuse as main transcript	c.4509T>C	p.Pro1503=	synonymous_variant	4/5	1		ENSP00000480284	P1
NEXMIF	ENST00000642681.2 linkuse as main transcript	c.*649T>C		3_prime_UTR_variant	3/3			ENSP00000495800

Frequencies

GnomAD3 genomes

AF:

0.000516

AC:

AN:

110384

Hom.:

Cov.:

AF XY:

0.000307

AC XY:

AN XY:

32590

show subpopulations

Gnomad AFR

AF:

0.000198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000984

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:

0.000946

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000614

AC:

102

AN:

166139

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

54297

show subpopulations

Gnomad AFR exome

AF:

0.000321

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:

0.000127

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.000485

GnomAD4 exome

AF:

0.00110

AC:

1200

AN:

1087605

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

362

AN XY:

354997

show subpopulations

Gnomad4 AFR exome

AF:

0.0000772

Gnomad4 AMR exome

AF:

0.0000609

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000124

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.000591

GnomAD4 genome

AF:

0.000516

AC:

AN:

110437

Hom.:

Cov.:

AF XY:

0.000306

AC XY:

AN XY:

32653

show subpopulations

Gnomad4 AFR

AF:

0.000197

Gnomad4 AMR

AF:

0.0000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000946

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000578

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	NEXMIF: BP4, BS2 -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 17, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Oct 20, 2017	This alteration is classified as 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. -

NEXMIF-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.1

DANN

Benign

0.74

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