rs61741739

chrX-74742403-A-GchrX-74742403-A-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001008537.3(NEXMIF):c.2154T>C(p.Asn718=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000649 in 1,209,645 control chromosomes in the GnomAD database, including 3 homozygotes. There are 200 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., 100 hem., cov: 22)
  • Exomes 𝑓: 0.00037 (1 hom. 100 hem.)
• Consequence: NEXMIF NM_001008537.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.833

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-74742403-A-G is Benign according to our data. Variant chrX-74742403-A-G is described in ClinVar as [Benign]. Clinvar id is 474059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.833 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXMIF	NM_001008537.3	c.2154T>C	p.Asn718=	synonymous_variant	3/4	ENST00000055682.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXMIF	ENST00000055682.12	c.2154T>C	p.Asn718=	synonymous_variant	3/4	1	NM_001008537.3	P1
NEXMIF	ENST00000616200.2	c.2154T>C	p.Asn718=	synonymous_variant	3/5	1		P1
NEXMIF	ENST00000642681.2	c.2154T>C	p.Asn718=	synonymous_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 380 AN: 111602 Hom.: 2 Cov.: 22 AF XY: 0.00302 AC XY: 102 AN XY: 33788

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000953

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000375

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00399

GnomAD3 exomes AF: 0.000953 AC: 174 AN: 182555 Hom.: 1 AF XY: 0.000505 AC XY: 34 AN XY: 67363

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.000370 AC: 406 AN: 1097989 Hom.: 1 Cov.: 31 AF XY: 0.000275 AC XY: 100 AN XY: 363371

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.000483

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: 0.00000119

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.00339 AC: 379 AN: 111656 Hom.: 2 Cov.: 22 AF XY: 0.00295 AC XY: 100 AN XY: 33852

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.000952

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000376

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00394

Alfa AF: 0.000261 Hom.: 1

Bravo AF: 0.00405

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 13, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 14, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2014

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	4.9
Dann	Benign	0.59

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: rs61741739; hg19: chrX-73962238;