chrX-74739480-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001008537.3(NEXMIF):​c.4476C>G​(p.Leu1492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Consequence

NEXMIF
NM_001008537.3 synonymous

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP7
Synonymous conserved (PhyloP=2.51 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXMIFNM_001008537.3 linkuse as main transcriptc.4476C>G p.Leu1492= 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.4476C>G p.Leu1492= synonymous_variant 4/41 NM_001008537.3 ENSP00000055682 P1
NEXMIFENST00000616200.2 linkuse as main transcriptc.4476C>G p.Leu1492= synonymous_variant 4/51 ENSP00000480284 P1
NEXMIFENST00000642681.2 linkuse as main transcriptc.*616C>G 3_prime_UTR_variant 3/3 ENSP00000495800

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
21

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

See cases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaNov 05, 2018This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. This variant was detected in homozygous state. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
6.7
DANN
Benign
0.69

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.

Other links and lift over

dbSNP: rs2080094874; hg19: chrX-73959315; API