chrX-74915899-T-C

Position:

• chrX-74915899-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.-48+8984A>G		intron_variant		ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEXMIF	ENST00000055682.12	c.-48+8984A>G		intron_variant		1	NM_001008537.3	ENSP00000055682.5
NEXMIF	ENST00000616200.2	c.-48+8984A>G		intron_variant		1		ENSP00000480284.1
NEXMIF	ENST00000642681.2	c.-48+8984A>G		intron_variant				ENSP00000495800.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 37944 AN: 110565 Hom.: 8853 Cov.: 22 AF XY: 0.333 AC XY: 10916 AN XY: 32805

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

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.293

Alfa AF: 0.198 Hom.: 3351

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

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

Other links and lift over

dbSNP: rs2211463; hg19: chrX-74135734;