Genetic Variant ENST00000640298.3:c.-1187C>T (chrX-119943590-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000640298.3(RHOXF1P3):c.-1187C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,069,153 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 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: not found (cov: 23)

Exomes 𝑓: 0.0000056 ( 0 hom. 4 hem. )

Consequence

RHOXF1P3
ENST00000640298.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.723

Publications

0 publications found

Variant links:

Genes affected

RHOXF1P3 (HGNC:51612): (Rhox homeobox family member 1 pseudogene 3)

RHOXF1P3 links:

NKAP (HGNC:29873): (NFKB activating protein) This gene encodes a protein that is involved in the activation of the ubiquitous transcription factor NF-kappaB. This protein is associated with the the histone deacetylase HDAC3 and with the Notch corepressor complex, and it thereby acts as a transcriptional repressor of Notch target genes. It is also required for alphabeta T cell development. A related pseudogene has been identified on chromosome X, while a related and intronless retrocopy, which has an intact CDS and may be functional, is located on chromosome 6. [provided by RefSeq, May 2010]

NKAP Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

NKAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035286635).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000640298.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAP	NM_024528.4	MANE Select	c.16G>A	p.Gly6Ser	missense	Exon 1 of 9	NP_078804.2	Q8N5F7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHOXF1P3	ENST00000640298.3	TSL:5	c.-1187C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000515421.1	A0A994J3T1
NKAP	ENST00000371410.5	TSL:1 MANE Select	c.16G>A	p.Gly6Ser	missense	Exon 1 of 9	ENSP00000360464.3	Q8N5F7
RHOXF1P3	ENST00000640298.3	TSL:5	c.-1187C>T		5_prime_UTR	Exon 1 of 5	ENSP00000515421.1	A0A994J3T1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000661

AC:

AN:

151268

AF XY:

0.0000205

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000561

AC:

AN:

1069153

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

344299

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25947

American (AMR)

AF:

0.00

AC:

AN:

33129

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17597

East Asian (EAS)

AF:

0.00

AC:

AN:

29825

South Asian (SAS)

AF:

0.000120

AC:

AN:

49893

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3874

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

825953

Other (OTH)

AF:

0.00

AC:

AN:

44797

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Cov.:

ExAC

AF:

0.0000167

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.99

CADD

Benign

8.1

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0043

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.74

M_CAP

Benign

0.0081

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

PhyloP100

-0.72

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.080

REVEL

Benign

0.017

Sift

Benign

0.096

Sift4G

Benign

0.91

Polyphen

0.0020

Vest4

0.066

MutPred

0.23

Gain of phosphorylation at G6 (P = 3e-04)

MVP

0.35

MPC

0.46

ClinPred

0.099

GERP RS

-6.2

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.23

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over