X-74740311-G-C

Position:

• chrX-74740311-G-C

Variant summary

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

The NM_001008537.3(NEXMIF):​c.4246C>G​(p.Pro1416Ala) 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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1416S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: NEXMIF NM_001008537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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=0.09796989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXMIF	NM_001008537.3	c.4246C>G	p.Pro1416Ala	missense_variant	3/4	ENST00000055682.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXMIF	ENST00000055682.12	c.4246C>G	p.Pro1416Ala	missense_variant	3/4	1	NM_001008537.3	P1
NEXMIF	ENST00000616200.2	c.4246C>G	p.Pro1416Ala	missense_variant	3/5	1		P1
NEXMIF	ENST00000642681.2	c.4246C>G	p.Pro1416Ala	missense_variant	3/3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.3
DANN	Benign	0.34
DEOGEN2	Benign	0.025	T;T;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.56	.;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.15	N;.;.
REVEL	Benign	0.055
Sift	Benign	0.30	T;.;.
Sift4G	Benign	0.42	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.11
MutPred		0.092		Gain of catalytic residue at P1416 (P = 0.0298);Gain of catalytic residue at P1416 (P = 0.0298);Gain of catalytic residue at P1416 (P = 0.0298);
MVP		0.12
MPC		0.22
ClinPred		0.13	T
GERP RS		0.95
Varity_R		0.033
gMVP		0.033

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: rs143577015; hg19: chrX-73960146;