20-45513755-A-G

Position:

• chr20-45513755-A-G

Variant summary

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

The NM_006652.2(SPINT3):​c.77-911T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,822 control chromosomes in the GnomAD database, including 38,308 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 0.71 (38308 hom., cov: 33)
• Consequence: SPINT3 NM_006652.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

Genes affected

SPINT3 (HGNC:11248): (serine peptidase inhibitor, Kunitz type 3) Predicted to enable receptor antagonist activity and transforming growth factor beta binding activity. Predicted to be involved in negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LOC107987282 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINT3	NM_006652.2	c.77-911T>C		intron_variant		ENST00000217428.7	NP_006643.1
LOC107987282	XR_001754641.3	n.100-19519A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINT3	ENST00000217428.7	c.77-911T>C		intron_variant		1	NM_006652.2	ENSP00000217428	P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107536 AN: 151704 Hom.: 38256 Cov.: 33

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.705

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.709 AC: 107651 AN: 151822 Hom.: 38308 Cov.: 33 AF XY: 0.706 AC XY: 52376 AN XY: 74196

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.705

Alfa AF: 0.688 Hom.: 73805

Bravo AF: 0.718

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.92
DANN	Benign	0.53

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: rs6130852; hg19: chr20-44142395;