Genetic Variant NFXL1:p.Gln794Arg (chr4-47855099-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001278624.2(NFXL1):c.2381A>G(p.Gln794Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000635 in 1,573,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

NFXL1
NM_001278624.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

Publications

0 publications found

Variant links:

Genes affected

NFXL1 (HGNC:18726): (nuclear transcription factor, X-box binding like 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NFXL1 links:

ENSG00000282917 (HGNC:58782):

ENSG00000282917 links:

LOC101927179 (HGNC:):

LOC101927179 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3244205).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278624.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFXL1	NM_001278624.2	MANE Select	c.2381A>G	p.Gln794Arg	missense	Exon 20 of 23	NP_001265553.1	Q6ZNB6-1
NFXL1	NM_001278623.1		c.2381A>G	p.Gln794Arg	missense	Exon 20 of 23	NP_001265552.1	Q6ZNB6-1
NFXL1	NM_152995.6		c.2381A>G	p.Gln794Arg	missense	Exon 20 of 23	NP_694540.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFXL1	ENST00000507489.2	TSL:1 MANE Select	c.2381A>G	p.Gln794Arg	missense	Exon 20 of 23	ENSP00000422037.1	Q6ZNB6-1
NFXL1	ENST00000329043.7	TSL:1	c.2381A>G	p.Gln794Arg	missense	Exon 20 of 23	ENSP00000333113.4	Q6ZNB6-1
NFXL1	ENST00000464756.6	TSL:1	n.*359A>G		non_coding_transcript_exon	Exon 21 of 24	ENSP00000425812.1	Q6ZNB6-2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.00000828

AC:

AN:

241596

AF XY:

0.00000763

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000422

AC:

AN:

1422018

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709076

show subpopulations

African (AFR)

AF:

0.0000622

AC:

AN:

32170

American (AMR)

AF:

0.0000234

AC:

AN:

42740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25638

East Asian (EAS)

AF:

0.00

AC:

AN:

38656

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1082024

Other (OTH)

AF:

0.00

AC:

AN:

58872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151672

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67876

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

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:

0.0000329

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.042

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

M_CAP

Benign

0.016

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

6.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.60

REVEL

Benign

0.13

Sift

Benign

0.23

Sift4G

Benign

0.41

Polyphen

0.041

Vest4

0.58

MutPred

0.47

Loss of catalytic residue at Q794 (P = 0.0084)

MVP

0.62

MPC

0.36

ClinPred

0.40

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.51

Mutation Taster

=57/43

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over