X-119943590-C-G

Variant names:

• chrX-119943590-C-G
• rs368205896
• NM_024528.4:c.16G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024528.4(NKAP):​c.16G>C​(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: NKAP NM_024528.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 0 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018822938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024528.4. 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>C	p.Gly6Arg	missense	Exon 1 of 9	NP_078804.2	Q8N5F7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAP	ENST00000371410.5	TSL:1 MANE Select	c.16G>C	p.Gly6Arg	missense	Exon 1 of 9	ENSP00000360464.3	Q8N5F7
	RHOXF1P3	ENST00000640298.3	TSL:5	c.-1187C>G		5_prime_UTR	Exon 1 of 5	ENSP00000515421.1	A0A994J3T1
	NKAP	ENST00000652253.1		c.13G>C	p.Gly5Arg	missense	Exon 1 of 9	ENSP00000498376.1	A0A494C050

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 151268 AF XY: 0.00

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 Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.77
DEOGEN2	Benign	0.0028	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.18	N
PhyloP100		-0.72
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.038
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.20		Gain of MoRF binding (P = 0.0065)
MVP		0.12
MPC		0.55
ClinPred		0.038	T
GERP RS		-6.2
PromoterAI		-0.085	Neutral
Varity_R		0.040
gMVP		0.18
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs368205896; hg19: chrX-119077553;