rs751841142

Variant names:

• chrX-74739491-C-A
• NM_001008537.3:c.4465G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-74739491-C-A
• chrX-74739491-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008537.3(NEXMIF):​c.4465G>T​(p.Asp1489Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,074,331 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
• Consequence: NEXMIF NM_001008537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19068652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.4465G>T	p.Asp1489Tyr	missense_variant	Exon 4 of 4	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEXMIF	ENST00000055682.12	c.4465G>T	p.Asp1489Tyr	missense_variant	Exon 4 of 4	1	NM_001008537.3	ENSP00000055682.5
NEXMIF	ENST00000616200.2	c.4465G>T	p.Asp1489Tyr	missense_variant	Exon 4 of 5	1		ENSP00000480284.1
NEXMIF	ENST00000642681	c.*605G>T		3_prime_UTR_variant	Exon 3 of 3			ENSP00000495800.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.31e-7 AC: 1 AN: 1074331 Hom.: 0 Cov.: 25 AF XY: 0.00000293 AC XY: 1 AN XY: 341813

Gnomad4 AFR exome AF: 0.00

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: 0.0000221

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.019	D;D
Polyphen		0.95	P;P
Vest4		0.48
MutPred		0.31		Loss of disorder (P = 0.0519);Loss of disorder (P = 0.0519);
MVP		0.21
MPC		0.55
ClinPred		0.67	D
GERP RS		0.63
Varity_R		0.21
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-73959326;