chr16-50639550-C-T

Variant names:

• chr16-50639550-C-T
• rs749986
• NM_033119.5:c.*5769C>T

Variant summary

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

The NM_033119.5(NKD1):​c.*5769C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,046 control chromosomes in the GnomAD database, including 29,386 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 0.62 (29376 hom., cov: 32)
  • Exomes 𝑓: 0.67 (10 hom.)
• Consequence: NKD1 NM_033119.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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 rank	MANE	Protein	UniProt
NKD1	NM_033119.5	c.*5769C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000268459.6	NP_149110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKD1	ENST00000268459.6	c.*5769C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_033119.5	ENSP00000268459.3

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93478 AN: 151874 Hom.: 29365 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.667 AC: 36 AN: 54 Hom.: 10 Cov.: 0 AF XY: 0.658 AC XY: 25 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.738 AC: 31 AN: 42

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.615 AC: 93521 AN: 151992 Hom.: 29376 Cov.: 32 AF XY: 0.615 AC XY: 45721 AN XY: 74298

African (AFR) AF: 0.535 AC: 22133 AN: 41404

American (AMR) AF: 0.556 AC: 8499 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2754 AN: 5150

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4816

European-Finnish (FIN) AF: 0.751 AC: 7945 AN: 10580

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.669 AC: 45459 AN: 67976

Other (OTH) AF: 0.604 AC: 1274 AN: 2110

Alfa AF: 0.646 Hom.: 3820

Bravo AF: 0.597

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.71
PhyloP100		-0.45

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: rs749986; hg19: chr16-50673461;