rs2209549

Positions:

• chrX-74738794-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008537.3(NEXMIF):​c.*611C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.66 (20750 hom., 19129 hem., cov: 20)
  • Exomes 𝑓: 0.86 (67 hom. 110 hem.)
  • Failed GnomAD Quality Control
• Consequence: NEXMIF NM_001008537.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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=-0.77).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.*611C>T		3_prime_UTR_variant	4/4	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEXMIF	ENST00000055682.12	c.*611C>T		3_prime_UTR_variant	4/4	1	NM_001008537.3	ENSP00000055682	P1
NEXMIF	ENST00000616200.2	c.*36+575C>T		intron_variant		1		ENSP00000480284	P1
NEXMIF	ENST00000642681.2	c.*1302C>T		3_prime_UTR_variant	3/3			ENSP00000495800

Frequencies

GnomAD3 genomes AF: 0.662 AC: 70579 AN: 106613 Hom.: 20765 Cov.: 20 AF XY: 0.654 AC XY: 19112 AN XY: 29223

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.863 AC: 259 AN: 300 Hom.: 67 Cov.: 0 AF XY: 0.873 AC XY: 110 AN XY: 126

Gnomad4 FIN exome AF: 0.861

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.662 AC: 70565 AN: 106654 Hom.: 20750 Cov.: 20 AF XY: 0.653 AC XY: 19129 AN XY: 29274

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.705

Alfa AF: 0.820 Hom.: 39136

Bravo AF: 0.625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.96
DANN	Benign	0.64

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: rs2209549; hg19: chrX-73958629; COSMIC: COSV50037133; COSMIC: COSV50037133;