X-74915899-T-C

Variant names:

• chrX-74915899-T-C
• rs2211463
• NM_001008537.3:c.-48+8984A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008537.3(NEXMIF):​c.-48+8984A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 110,618 control chromosomes in the GnomAD database, including 8,865 homozygotes. There are 10,965 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8865 hom., 10965 hem., cov: 22)
• Consequence: NEXMIF NM_001008537.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• X-linked intellectual disability, Cantagrel type

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.-48+8984A>G		intron_variant	Intron 1 of 3	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEXMIF	ENST00000055682.12	c.-48+8984A>G		intron_variant	Intron 1 of 3	1	NM_001008537.3	ENSP00000055682.5
NEXMIF	ENST00000616200.2	c.-48+8984A>G		intron_variant	Intron 1 of 4	1		ENSP00000480284.1
NEXMIF	ENST00000642681.2	c.-48+8984A>G		intron_variant	Intron 1 of 2			ENSP00000495800.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 37944 AN: 110565 Hom.: 8853 Cov.: 22

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 38015 AN: 110618 Hom.: 8865 Cov.: 22 AF XY: 0.334 AC XY: 10965 AN XY: 32868

African (AFR) AF: 0.791 AC: 23909 AN: 30232

American (AMR) AF: 0.342 AC: 3547 AN: 10365

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 287 AN: 2628

East Asian (EAS) AF: 0.931 AC: 3217 AN: 3457

South Asian (SAS) AF: 0.470 AC: 1196 AN: 2546

European-Finnish (FIN) AF: 0.0827 AC: 496 AN: 5994

Middle Eastern (MID) AF: 0.126 AC: 27 AN: 215

European-Non Finnish (NFE) AF: 0.0921 AC: 4880 AN: 52985

Other (OTH) AF: 0.293 AC: 444 AN: 1514

Alfa AF: 0.205 Hom.: 4045

Bravo AF: 0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2211463; hg19: chrX-74135734;