rs774654591

Variant names:

• chrX-74740268-T-A
• rs774654591
• NM_001008537.3:c.4289A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-74740268-T-A
• chrX-74740268-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001008537.3(NEXMIF):​c.4289A>T​(p.Lys1430Met) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: NEXMIF NM_001008537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27626556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.4289A>T	p.Lys1430Met	missense_variant	Exon 3 of 4	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEXMIF	ENST00000055682.12	c.4289A>T	p.Lys1430Met	missense_variant	Exon 3 of 4	1	NM_001008537.3	ENSP00000055682.5
NEXMIF	ENST00000616200.2	c.4289A>T	p.Lys1430Met	missense_variant	Exon 3 of 5	1		ENSP00000480284.1
NEXMIF	ENST00000642681.2	c.4289A>T	p.Lys1430Met	missense_variant	Exon 3 of 3			ENSP00000495800.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;T;.
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	.;T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.74	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.27	N;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;.;.
Sift4G	Benign	0.11	T;T;.
Polyphen		1.0	D;D;.
Vest4		0.32
MutPred		0.15		Loss of ubiquitination at K1430 (P = 9e-04);Loss of ubiquitination at K1430 (P = 9e-04);Loss of ubiquitination at K1430 (P = 9e-04);
MVP		0.18
MPC		0.91
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.17
gMVP		0.19

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: rs774654591; hg19: chrX-73960103;