dbSNP rs2209549: NEXMIF:c.*611C>T (chrX-74738794-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001008537.3(NEXMIF):c.*611C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.66 ( 20750 hom., 19129 hem., cov: 20)

Exomes 𝑓: 0.86 ( 67 hom. 110 hem. )

Failed GnomAD Quality Control

Consequence

NEXMIF
NM_001008537.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.246

Publications

4 publications found

Variant links:

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]

NEXMIF Gene-Disease associations (from GenCC):

X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
X-linked intellectual disability, Cantagrel type
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
myoclonic-astatic epilepsy
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

NEXMIF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency = 1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEXMIF	NM_001008537.3 link	c.*611C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000055682.12	NP_001008537.1	Q5QGS0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEXMIF	ENST00000055682.12 link	c.*611C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_001008537.3	ENSP00000055682.5	Q5QGS0
NEXMIF	ENST00000616200.2 link	c.*36+575C>T	intron_variant	Intron 4 of 4	1		ENSP00000480284.1	Q5QGS0
NEXMIF	ENST00000642681.2 link	c.*1302C>T	3_prime_UTR_variant	Exon 3 of 3			ENSP00000495800.1	A0A2R8YEQ5

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

70579

AN:

106613

Hom.:

20765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.981

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.893

Gnomad EAS

AF:

0.0363

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.885

Gnomad MID

AF:

0.869

Gnomad NFE

AF:

0.904

Gnomad OTH

AF:

0.715

GnomAD4 exome

AF:

0.863

AC:

259

AN:

300

Hom.:

Cov.:

AF XY:

0.873

AC XY:

110

AN XY:

126

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.861

AC:

255

AN:

296

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.662

AC:

70565

AN:

106654

Hom.:

20750

Cov.:

AF XY:

0.653

AC XY:

19129

AN XY:

29274

show subpopulations

African (AFR)

AF:

0.255

AC:

7494

AN:

29413

American (AMR)

AF:

0.651

AC:

6385

AN:

9801

Ashkenazi Jewish (ASJ)

AF:

0.893

AC:

2295

AN:

2571

East Asian (EAS)

AF:

0.0364

AC:

124

AN:

3406

South Asian (SAS)

AF:

0.504

AC:

1220

AN:

2420

European-Finnish (FIN)

AF:

0.885

AC:

4460

AN:

5041

Middle Eastern (MID)

AF:

0.865

AC:

180

AN:

208

European-Non Finnish (NFE)

AF:

0.904

AC:

46737

AN:

51686

Other (OTH)

AF:

0.705

AC:

1014

AN:

1439

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

485

970

1454

1939

2424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.792

Hom.:

53032

Bravo

AF:

0.625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.96

(source)

DANN

Benign

0.64

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over