rs749985

Positions:

• chr16-50639740-T-C
• chr16-50639740-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033119.5(NKD1):​c.*5959T>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 0.629 in 152,108 control chromosomes in the GnomAD database, including 30,554 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 0.63 (30552 hom., cov: 32)
  • Exomes 𝑓: 0.45 (2 hom.)
• Consequence: NKD1 NM_033119.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKD1	NM_033119.5	c.*5959T>C		3_prime_UTR_variant	10/10	ENST00000268459.6	NP_149110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKD1	ENST00000268459.6	c.*5959T>C		3_prime_UTR_variant	10/10	1	NM_033119.5	ENSP00000268459	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95635 AN: 151968 Hom.: 30538 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.357 AC XY: 5 AN XY: 14

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.629 AC: 95681 AN: 152086 Hom.: 30552 Cov.: 32 AF XY: 0.629 AC XY: 46750 AN XY: 74336

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.609

Alfa AF: 0.651 Hom.: 32549

Bravo AF: 0.613

Asia WGS AF: 0.509 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
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

Other links and lift over

dbSNP: rs749985; hg19: chr16-50673651;