20-45513755-A-G

Variant names:

• chr20-45513755-A-G
• rs6130852
• NM_006652.2:c.77-911T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ENSG00000237464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006652.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT3	NM_006652.2	MANE Select	c.77-911T>C		intron	N/A	NP_006643.1	P49223

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT3	ENST00000217428.7	TSL:1 MANE Select	c.77-911T>C		intron	N/A	ENSP00000217428.6	P49223
	ENSG00000237464	ENST00000803561.1		n.120-19519A>G		intron	N/A
	ENSG00000237464	ENST00000803562.1		n.127-19519A>G		intron	N/A

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

African (AFR) AF: 0.764 AC: 31673 AN: 41440

American (AMR) AF: 0.734 AC: 11208 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3298 AN: 5148

South Asian (SAS) AF: 0.628 AC: 3022 AN: 4812

European-Finnish (FIN) AF: 0.682 AC: 7174 AN: 10520

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 46924 AN: 67848

Other (OTH) AF: 0.705 AC: 1486 AN: 2108

Alfa AF: 0.696 Hom.: 118428

Bravo AF: 0.718

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.92
DANN	Benign	0.53
PhyloP100		-0.17
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: rs6130852; hg19: chr20-44142395;