Genetic Variant RHOXF1P3:c.-1187C>T (chrX-119943590-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAP	NM_024528.4 link	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 9	ENST00000371410.5	NP_078804.2	Q8N5F7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHOXF1P3	ENST00000640298.3 link	c.-1187C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	5		ENSP00000515421.1	A0A994J3T1
NKAP	ENST00000371410.5 link	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 9	1	NM_024528.4	ENSP00000360464.3	Q8N5F7
RHOXF1P3	ENST00000640298.3 link	c.-1187C>T		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000515421.1	A0A994J3T1
NKAP	ENST00000652253.1 link	c.13G>A	p.Gly5Ser	missense_variant	Exon 1 of 9			ENSP00000498376.1	A0A494C050

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000661

AC:

AN:

151268

Hom.:

AF XY:

0.0000205

AC XY:

AN XY:

48838

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 SAS exome

AF:

0.0000729

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000167

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.99

CADD

Benign

8.1

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over