X-74739489-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001008537.3(NEXMIF):​c.4467C>T​(p.Asp1489=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000169 in 1,186,410 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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., 0 hem., cov: 21)
Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

NEXMIF
NM_001008537.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant X-74739489-G-A is Benign according to our data. Variant chrX-74739489-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1130192.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEXMIFNM_001008537.3 linkuse as main transcriptc.4467C>T p.Asp1489= synonymous_variant 4/4 ENST00000055682.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEXMIFENST00000055682.12 linkuse as main transcriptc.4467C>T p.Asp1489= synonymous_variant 4/41 NM_001008537.3 P1
NEXMIFENST00000616200.2 linkuse as main transcriptc.4467C>T p.Asp1489= synonymous_variant 4/51 P1
NEXMIFENST00000642681.2 linkuse as main transcriptc.*607C>T 3_prime_UTR_variant 3/3

Frequencies

GnomAD3 genomes
AF:
0.00000916
AC:
1
AN:
109111
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
31383
show subpopulations
Gnomad AFR
AF:
0.0000334
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
2
AN:
166812
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
53910
show subpopulations
Gnomad AFR exome
AF:
0.000162
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.28e-7
AC:
1
AN:
1077299
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
344437
show subpopulations
Gnomad4 AFR exome
AF:
0.0000387
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000916
AC:
1
AN:
109111
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
31383
show subpopulations
Gnomad4 AFR
AF:
0.0000334
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
7.9
DANN
Benign
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs373339344; hg19: chrX-73959324; API