20-45749938-T-C

Position:

• chr20-45749938-T-C

Variant summary

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

The ENST00000448174.1(SPINT5P):​n.19T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 169,542 control chromosomes in the GnomAD database, including 31,651 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 0.61 (28559 hom., cov: 32)
  • Exomes 𝑓: 0.59 (3092 hom.)
• Consequence: SPINT5P ENST00000448174.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

SPINT5P (HGNC:16161): (serine peptidase inhibitor, Kunitz type 5, pseudogene)

WFDC3 (HGNC:15957): (WAP four-disulfide core domain 3) This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. The WFDC domain, or WAP signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor. The encoded protein contains four WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Alternatively spliced transcript variants have been observed but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINT5P	ENST00000448174.1	n.19T>C		non_coding_transcript_exon_variant	1/1
WFDC3	ENST00000481847.5	n.520-1524A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92475 AN: 151796 Hom.: 28516 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.586 AC: 10334 AN: 17628 Hom.: 3092 Cov.: 0 AF XY: 0.591 AC XY: 4971 AN XY: 8412

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.609 AC: 92579 AN: 151914 Hom.: 28559 Cov.: 32 AF XY: 0.605 AC XY: 44917 AN XY: 74250

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.580

Alfa AF: 0.621 Hom.: 17063

Bravo AF: 0.615

Asia WGS AF: 0.525 AC: 1828 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	5.0
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs380421; hg19: chr20-44378577; COSMIC: COSV71391138;