chrX-74739427-C-G

Variant names:

• chrX-74739427-C-G
• NM_001008537.3:c.4529G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001008537.3(NEXMIF):​c.4529G>C​(p.Arg1510Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,552 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: NEXMIF NM_001008537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03323978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.4529G>C	p.Arg1510Pro	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.4529G>C	p.Arg1510Pro	missense_variant	Exon 4 of 4	1	NM_001008537.3	ENSP00000055682.5
NEXMIF	ENST00000616200.2	c.4529G>C	p.Arg1510Pro	missense_variant	Exon 4 of 5	1		ENSP00000480284.1
NEXMIF	ENST00000642681	c.*669G>C		3_prime_UTR_variant	Exon 3 of 3			ENSP00000495800.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083552 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 351320

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: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.7
DANN	Benign	0.70
DEOGEN2	Benign	0.019	T;T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.53	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.050	N;.
REVEL	Benign	0.23
Sift	Benign	0.19	T;.
Sift4G	Benign	0.23	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.28		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.44
MPC		0.32
ClinPred		0.041	T
GERP RS		-8.2
Varity_R		0.14
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-73959262;