chr6-28260017-T-C

Position:

• chr6-28260017-T-C

Variant summary

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

The NM_001007531.3(NKAPL):​c.646T>C​(p.Ser216Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NKAPL NM_001007531.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.248

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=0.05821401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAPL	NM_001007531.3	c.646T>C	p.Ser216Pro	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.646T>C	p.Ser216Pro	missense_variant	1/1	6	NM_001007531.3	ENSP00000345716.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.646T>C (p.S216P) alteration is located in exon 1 (coding exon 1) of the NKAPL gene. This alteration results from a T to C substitution at nucleotide position 646, causing the serine (S) at amino acid position 216 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.60
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.021
Sift	Benign	0.13	T
Sift4G	Benign	0.064	T
Polyphen		0.0010	B
Vest4		0.083
MutPred		0.28		Loss of phosphorylation at S216 (P = 9e-04);
MVP		0.040
MPC		0.55
ClinPred		0.046	T
GERP RS		1.9
Varity_R		0.27
gMVP		0.015

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-28227795;