Genetic Variant NKD1:c.259+183T>C (chr16-50608543-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033119.5(NKD1):c.259+183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 629,242 control chromosomes in the GnomAD database, including 1,393 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.075 ( 966 hom., cov: 32)

Exomes 𝑓: 0.024 ( 427 hom. )

Consequence

NKD1
NM_033119.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.74

Publications

1 publications found

Variant links:

Genes affected

NKD1 (HGNC:17045): (NKD inhibitor of WNT signaling pathway 1) In the mouse, Nkd is a Dishevelled (see DVL1; MIM 601365)-binding protein that functions as a negative regulator of the Wnt (see WNT1; MIM 164820)-beta-catenin (see MIM 116806)-Tcf (see MIM 602272) signaling pathway.[supplied by OMIM, Jun 2003]

NKD1 links:

ENSG00000205414 (HGNC:58215):

ENSG00000205414 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKD1	NM_033119.5 link	c.259+183T>C		intron_variant	Intron 4 of 9	ENST00000268459.6	NP_149110.1
NKD1-AS1	XR_007065197.1 link	n.61-93A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NKD1	ENST00000268459.6 link	c.259+183T>C	intron_variant	Intron 4 of 9	1	NM_033119.5	ENSP00000268459.3
ENSG00000205414	ENST00000379963.1 link	n.95-93A>G	intron_variant	Intron 1 of 1	2
NKD1	ENST00000564336.1 link	n.417+183T>C	intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0743

AC:

11296

AN:

151944

Hom.:

948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0426

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.0301

Gnomad SAS

AF:

0.00892

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0637

GnomAD4 exome

AF:

0.0244

AC:

11642

AN:

477180

Hom.:

427

AF XY:

0.0222

AC XY:

5609

AN XY:

252264

show subpopulations

African (AFR)

AF:

0.191

AC:

2724

AN:

14252

American (AMR)

AF:

0.0497

AC:

1498

AN:

30122

Ashkenazi Jewish (ASJ)

AF:

0.0313

AC:

482

AN:

15420

East Asian (EAS)

AF:

0.0236

AC:

726

AN:

30708

South Asian (SAS)

AF:

0.00851

AC:

446

AN:

52392

European-Finnish (FIN)

AF:

0.0213

AC:

643

AN:

30144

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

2110

European-Non Finnish (NFE)

AF:

0.0156

AC:

4294

AN:

275066

Other (OTH)

AF:

0.0298

AC:

803

AN:

26966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

515

1030

1546

2061

2576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0747

AC:

11356

AN:

152062

Hom.:

966

Cov.:

AF XY:

0.0728

AC XY:

5411

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.211

AC:

8754

AN:

41432

American (AMR)

AF:

0.0425

AC:

650

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3468

East Asian (EAS)

AF:

0.0300

AC:

155

AN:

5174

South Asian (SAS)

AF:

0.00851

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0265

AC:

281

AN:

10592

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0177

AC:

1205

AN:

67982

Other (OTH)

AF:

0.0630

AC:

133

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

464

928

1393

1857

2321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0612

Hom.:

122

Bravo

AF:

0.0825

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.34

(source)

DANN

Benign

0.44

PhyloP100

-2.7

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over