rs1635

Variant names:

• chr6-28259826-C-A
• rs1635
• NM_001007531.3:c.455C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-28259826-C-A
• chr6-28259826-C-G
• chr6-28259826-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007531.3(NKAPL):​c.455C>A​(p.Thr152Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,614,030 control chromosomes in the GnomAD database, including 9,995 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.14 (2381 hom., cov: 32)
  • Exomes 𝑓: 0.073 (7614 hom.)
• Consequence: NKAPL NM_001007531.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 62 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016289353).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAPL	NM_001007531.3	c.455C>A	p.Thr152Asn	missense_variant	Exon 1 of 1	ENST00000343684.4	NP_001007532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKAPL	ENST00000343684.4	c.455C>A	p.Thr152Asn	missense_variant	Exon 1 of 1	6	NM_001007531.3	ENSP00000345716.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21174 AN: 152054 Hom.: 2366 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.118 AC: 29563 AN: 251212 AF XY: 0.113

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.365

Gnomad FIN exome AF: 0.0411

Gnomad NFE exome AF: 0.0496

Gnomad OTH exome AF: 0.0816

GnomAD4 exome AF: 0.0733 AC: 107102 AN: 1461858 Hom.: 7614 Cov.: 35 AF XY: 0.0752 AC XY: 54721 AN XY: 727226

African (AFR) AF: 0.294 AC: 9855 AN: 33480

American (AMR) AF: 0.157 AC: 7038 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0970 AC: 2536 AN: 26134

East Asian (EAS) AF: 0.366 AC: 14538 AN: 39700

South Asian (SAS) AF: 0.156 AC: 13426 AN: 86252

European-Finnish (FIN) AF: 0.0424 AC: 2265 AN: 53406

Middle Eastern (MID) AF: 0.116 AC: 671 AN: 5768

European-Non Finnish (NFE) AF: 0.0463 AC: 51456 AN: 1111998

Other (OTH) AF: 0.0880 AC: 5317 AN: 60396

GnomAD4 genome AF: 0.140 AC: 21230 AN: 152172 Hom.: 2381 Cov.: 32 AF XY: 0.140 AC XY: 10449 AN XY: 74414

African (AFR) AF: 0.284 AC: 11777 AN: 41476

American (AMR) AF: 0.151 AC: 2317 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1789 AN: 5180

South Asian (SAS) AF: 0.162 AC: 782 AN: 4824

European-Finnish (FIN) AF: 0.0441 AC: 468 AN: 10604

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0499 AC: 3396 AN: 68012

Other (OTH) AF: 0.135 AC: 284 AN: 2106

Alfa AF: 0.0843 Hom.: 4753

Bravo AF: 0.155

TwinsUK AF: 0.0378 AC: 140

ALSPAC AF: 0.0488 AC: 188

ESP6500AA AF: 0.279 AC: 1231

ESP6500EA AF: 0.0537 AC: 462

ExAC AF: 0.118 AC: 14295

Asia WGS AF: 0.173 AC: 599 AN: 3478

EpiCase AF: 0.0513

EpiControl AF: 0.0516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.69
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Benign	0.096	T
Sift4G	Uncertain	0.057	T
Polyphen		0.0030	B
Vest4		0.023
MPC		0.49
ClinPred		0.0065	T
GERP RS		-0.57
Varity_R		0.14
gMVP		0.13
Mutation Taster		=98/2	polymorphism (auto)

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: rs1635; hg19: chr6-28227604; COSMIC: COSV59197162;