chrX-74739492-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001008537.3(NEXMIF):​c.4464C>A​(p.Ser1488=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,181,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 0.0000092 ( 0 hom., 1 hem., cov: 21)
Exomes 𝑓: 0.000021 ( 0 hom. 7 hem. )

Consequence

NEXMIF
NM_001008537.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.195
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant X-74739492-G-T is Benign according to our data. Variant chrX-74739492-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1141799.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.195 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXMIFNM_001008537.3 linkuse as main transcriptc.4464C>A p.Ser1488= synonymous_variant 4/4 ENST00000055682.12 NP_001008537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEXMIFENST00000055682.12 linkuse as main transcriptc.4464C>A p.Ser1488= synonymous_variant 4/41 NM_001008537.3 ENSP00000055682 P1
NEXMIFENST00000616200.2 linkuse as main transcriptc.4464C>A p.Ser1488= synonymous_variant 4/51 ENSP00000480284 P1
NEXMIFENST00000642681.2 linkuse as main transcriptc.*604C>A 3_prime_UTR_variant 3/3 ENSP00000495800

Frequencies

GnomAD3 genomes
AF:
0.00000921
AC:
1
AN:
108617
Hom.:
0
Cov.:
21
AF XY:
0.0000323
AC XY:
1
AN XY:
31005
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:
0.000287
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
4
AN:
165245
Hom.:
0
AF XY:
0.0000190
AC XY:
1
AN XY:
52651
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000157
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000272
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
22
AN:
1072757
Hom.:
0
Cov.:
25
AF XY:
0.0000206
AC XY:
7
AN XY:
340537
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000606
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000486
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000920
AC:
1
AN:
108667
Hom.:
0
Cov.:
21
AF XY:
0.0000322
AC XY:
1
AN XY:
31065
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000288
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 09, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
1.3
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs189355247; hg19: chrX-73959327; API