chr16-50608543-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033119.5(NKD1):​c.259+183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 477,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: NKD1 NM_033119.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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>A		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>A		intron	N/A	ENSP00000268459.3
	ENSG00000205414	ENST00000379963.1	TSL:2	n.95-93A>T		intron	N/A
	NKD1	ENST00000564336.1	TSL:3	n.417+183T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000629 AC: 3 AN: 477298 Hom.: 0 AF XY: 0.0000119 AC XY: 3 AN XY: 252324

African (AFR) AF: 0.00 AC: 0 AN: 14268

American (AMR) AF: 0.00 AC: 0 AN: 30132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15424

East Asian (EAS) AF: 0.00 AC: 0 AN: 30720

South Asian (SAS) AF: 0.0000382 AC: 2 AN: 52394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2110

European-Non Finnish (NFE) AF: 0.00000363 AC: 1 AN: 275116

Other (OTH) AF: 0.00 AC: 0 AN: 26980

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.57
PhyloP100		-2.7

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;