6-28259826-C-G

Position:

• chr6-28259826-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001007531.3(NKAPL):​c.455C>G​(p.Thr152Ser) 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. T152N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NKAPL NM_001007531.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05338335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAPL	NM_001007531.3	c.455C>G	p.Thr152Ser	missense_variant	1/1	ENST00000343684.4	NP_001007532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAPL	ENST00000343684.4	c.455C>G	p.Thr152Ser	missense_variant	1/1		NM_001007531.3	ENSP00000345716	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.23
DANN	Benign	0.53
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.33	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Polyphen		0.0060	B
Vest4		0.056
MutPred		0.18		Gain of relative solvent accessibility (P = 0.2363);
MVP		0.014
MPC		0.38
ClinPred		0.17	T
GERP RS		-0.57
Varity_R		0.087
gMVP		0.072

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: rs1635; hg19: chr6-28227604;