rs41298498

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001008537.3(NEXMIF):c.2598C>A(p.Ser866Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,209,789 control chromosomes in the GnomAD database, including 167 homozygotes. There are 7,772 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 17 hom., 565 hem., cov: 23)

Exomes 𝑓: 0.019 ( 150 hom. 7207 hem. )

Consequence

NEXMIF
NM_001008537.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.305

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-74741959-G-T is Benign according to our data. Variant chrX-74741959-G-T is described in ClinVar as [Benign]. Clinvar id is 129383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.305 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0157 (1752/111916) while in subpopulation SAS AF= 0.0464 (124/2672). AF 95% confidence interval is 0.0398. There are 17 homozygotes in gnomad4. There are 565 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 link	c.2598C>A	p.Ser866Ser	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.2598C>A	p.Ser866Ser	synonymous_variant	Exon 3 of 4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 link	c.2598C>A	p.Ser866Ser	synonymous_variant	Exon 3 of 5	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 link	c.2598C>A	p.Ser866Ser	synonymous_variant	Exon 3 of 3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

1752

AN:

111859

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

564

AN XY:

34017

show subpopulations

Gnomad AFR

AF:

0.00260

Gnomad AMI

AF:

0.00732

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.000562

Gnomad SAS

AF:

0.0459

Gnomad FIN

AF:

0.0410

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0126

GnomAD3 exomes

AF:

0.0206

AC:

3782

AN:

183174

Hom.:

AF XY:

0.0226

AC XY:

1533

AN XY:

67716

show subpopulations

Gnomad AFR exome

AF:

0.00205

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.000936

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0449

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0186

AC:

20424

AN:

1097873

Hom.:

150

Cov.:

AF XY:

0.0198

AC XY:

7207

AN XY:

363249

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.00150

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0486

Gnomad4 FIN exome

AF:

0.0423

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0178

GnomAD4 genome

AF:

0.0157

AC:

1752

AN:

111916

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

565

AN XY:

34084

show subpopulations

Gnomad4 AFR

AF:

0.00259

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.00189

Gnomad4 EAS

AF:

0.000564

Gnomad4 SAS

AF:

0.0464

Gnomad4 FIN

AF:

0.0410

Gnomad4 NFE

AF:

0.0206

Gnomad4 OTH

AF:

0.0125

Alfa

AF:

0.0154

Hom.:

117

Bravo

AF:

0.0134

EpiCase

AF:

0.0183

EpiControl

AF:

0.0182

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 30, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 01, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Nov 24, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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