rs12000

Positions:

• chr6-28259658-A-C
• chr6-28259658-A-G
• chr6-28259658-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007531.3(NKAPL):​c.287A>C​(p.Tyr96Ser) 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. 15/21 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. Y96C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NKAPL NM_001007531.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

Genes affected

NKAPL (HGNC:21584): (NFKB activating protein like) Predicted to enable chromatin binding activity. Predicted to be involved in regulation of gene expression. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08105114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKAPL	NM_001007531.3	c.287A>C	p.Tyr96Ser	missense_variant	1/1	ENST00000343684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKAPL	ENST00000343684.4	c.287A>C	p.Tyr96Ser	missense_variant	1/1		NM_001007531.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.8
DANN	Benign	0.68
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.0090
Sift	Benign	0.093	T
Sift4G	Benign	0.51	T
Polyphen		0.24	B
Vest4		0.26
MutPred		0.44		Loss of stability (P = 0.0241);
MVP		0.11
MPC		0.62
ClinPred		0.088	T
GERP RS		1.9
Varity_R		0.064
gMVP		0.13

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

Other links and lift over

dbSNP: rs12000; hg19: chr6-28227436;