chr11-62801631-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006362.5(NXF1):c.640C>G(p.Leu214Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00652 in 1,610,830 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 44 hom. )

Consequence

NXF1
NM_006362.5 missense, splice_region

Scores

Splicing: ADA: 0.0005218

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.00

Publications

11 publications found

Variant links:

Genes affected

NXF1 (HGNC:8071): (nuclear RNA export factor 1) This gene is one member of a family of nuclear RNA export factor genes. Common domain features of this family are a noncanonical RNP-type RNA-binding domain (RBD), 4 leucine-rich repeats (LRRs), a nuclear transport factor 2 (NTF2)-like domain that allows heterodimerization with NTF2-related export protein-1 (NXT1), and a ubiquitin-associated domain that mediates interactions with nucleoporins. The LRRs and NTF2-like domains are required for export activity. Alternative splicing seems to be a common mechanism in this gene family. The encoded protein of this gene shuttles between the nucleus and the cytoplasm and binds in vivo to poly(A)+ RNA. It is the vertebrate homologue of the yeast protein Mex67p. The encoded protein overcomes the mRNA export block caused by the presence of saturating amounts of CTE (constitutive transport element) RNA of type D retroviruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

NXF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007778913).

BP6

Variant 11-62801631-G-C is Benign according to our data. Variant chr11-62801631-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 773247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF1	NM_006362.5 link	c.640C>G	p.Leu214Val	missense_variant, splice_region_variant	Exon 7 of 21	ENST00000294172.7	NP_006353.2	Q9UBU9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF1	ENST00000294172.7 link	c.640C>G	p.Leu214Val	missense_variant, splice_region_variant	Exon 7 of 21	1	NM_006362.5	ENSP00000294172.2		Q9UBU9-1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

584

AN:

149704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00291

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00683

Gnomad OTH

AF:

0.00532

GnomAD2 exomes

AF:

0.00392

AC:

979

AN:

249792

AF XY:

0.00413

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.00655

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00679

AC:

9921

AN:

1461006

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

4789

AN XY:

726864

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33418

American (AMR)

AF:

0.00436

AC:

195

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26108

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.000302

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.000880

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00835

AC:

9280

AN:

1111366

Other (OTH)

AF:

0.00524

AC:

316

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

482

964

1445

1927

2409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00390

AC:

584

AN:

149824

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

247

AN XY:

73202

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

40144

American (AMR)

AF:

0.00290

AC:

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

5004

South Asian (SAS)

AF:

0.000213

AC:

AN:

4686

European-Finnish (FIN)

AF:

0.00105

AC:

AN:

10466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00683

AC:

462

AN:

67674

Other (OTH)

AF:

0.00527

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00520

Hom.:

Bravo

AF:

0.00419

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00830

AC:

ExAC

AF:

0.00375

AC:

455

EpiCase

AF:

0.00695

EpiControl

AF:

0.00742

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.15

.;T;T;.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

T;T;.;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0078

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.10

N;N;N;.;.

PhyloP100

4.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N;N;N;.

REVEL

Benign

0.12

Sift

Benign

0.22

T;T;T;T;.

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.0, 0.0070

.;B;B;B;B

Vest4

0.13

MVP

0.51

MPC

0.79

ClinPred

0.019

GERP RS

0.91

Varity_R

0.13

gMVP

0.16

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.086

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over