Genetic Variant NKD1:c.*2490G>C (chr16-50636271-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033119.5(NKD1):c.*2490G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,062 control chromosomes in the GnomAD database, including 28,287 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 0.60 ( 28280 hom., cov: 32)

Exomes 𝑓: 0.75 ( 7 hom. )

Consequence

NKD1
NM_033119.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.653

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKD1	NM_033119.5 link	c.*2490G>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000268459.6	NP_149110.1	Q969G9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKD1	ENST00000268459.6 link	c.*2490G>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_033119.5	ENSP00000268459.3		Q969G9

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91328

AN:

151920

Hom.:

28271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.790

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.594

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.722

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.601

AC:

91368

AN:

152038

Hom.:

28280

Cov.:

AF XY:

0.602

AC XY:

44780

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.538

Gnomad4 ASJ

AF:

0.683

Gnomad4 EAS

AF:

0.533

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.670

Gnomad4 OTH

AF:

0.596

Alfa

AF:

0.561

Hom.:

1821

Bravo

AF:

0.579

Asia WGS

AF:

0.490

AC:

1705

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.0

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over