NM_033119.5:c.259+183T>C

Variant names:

• chr16-50608543-T-C
• rs746702
• NM_033119.5:c.259+183T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 1 publications found

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]

ENSG00000205414 (HGNC:58215):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033119.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD1	NM_033119.5	MANE Select	c.259+183T>C		intron	N/A	NP_149110.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD1	ENST00000268459.6	TSL:1 MANE Select	c.259+183T>C		intron	N/A	ENSP00000268459.3
	ENSG00000205414	ENST00000379963.1	TSL:2	n.95-93A>G		intron	N/A
	NKD1	ENST00000564336.1	TSL:3	n.417+183T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11296 AN: 151944 Hom.: 948 Cov.: 32

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

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: 26 AN: 2110

European-Non Finnish (NFE) AF: 0.0156 AC: 4294 AN: 275066

Other (OTH) AF: 0.0298 AC: 803 AN: 26966

GnomAD4 genome AF: 0.0747 AC: 11356 AN: 152062 Hom.: 966 Cov.: 32 AF XY: 0.0728 AC XY: 5411 AN XY: 74360

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: 41 AN: 4818

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0177 AC: 1205 AN: 67982

Other (OTH) AF: 0.0630 AC: 133 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
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)

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: rs746702; hg19: chr16-50642454;