rs1031348126

chrX-74742260-C-AchrX-74742260-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.2297G>T(p.Gly766Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 111,893 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G766E) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
• Consequence: NEXMIF NM_001008537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

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=0.18997061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXMIF	NM_001008537.3	c.2297G>T	p.Gly766Val	missense_variant	3/4	ENST00000055682.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXMIF	ENST00000055682.12	c.2297G>T	p.Gly766Val	missense_variant	3/4	1	NM_001008537.3	P1
NEXMIF	ENST00000616200.2	c.2297G>T	p.Gly766Val	missense_variant	3/5	1		P1
NEXMIF	ENST00000642681.2	c.2297G>T	p.Gly766Val	missense_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111893 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 34069

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111893 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 34069

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000950

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	9.7
Dann	Benign	0.83
DEOGEN2	Benign	0.024	T;T;.
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.043
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.18	T;T;.
Polyphen		0.30	B;B;.
Vest4		0.16
MutPred		0.082		Loss of catalytic residue at I764 (P = 0.1551);Loss of catalytic residue at I764 (P = 0.1551);Loss of catalytic residue at I764 (P = 0.1551);
MVP		0.11
MPC		0.35
ClinPred		0.28	T
GERP RS		4.3
Varity_R		0.22
gMVP		0.14

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: rs1031348126; hg19: chrX-73962095;