rs151265860

Variant names:

• chr20-45515547-G-A
• rs151265860
• NM_006652.2:c.62C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-45515547-G-A
• chr20-45515547-G-C
• chr20-45515547-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006652.2(SPINT3):​c.62C>T​(p.Ser21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,548,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SPINT3 NM_006652.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.300
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07664806).

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.62C>T	p.Ser21Leu	missense	Exon 1 of 2	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.62C>T	p.Ser21Leu	missense	Exon 1 of 2	ENSP00000217428.6	P49223
	ENSG00000237464	ENST00000803561.1		n.120-17727G>A		intron	N/A
	ENSG00000237464	ENST00000803562.1		n.127-17727G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149744 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000236 AC: 33 AN: 1398932 Hom.: 0 Cov.: 32 AF XY: 0.0000232 AC XY: 16 AN XY: 689980

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.00 AC: 0 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000287 AC: 31 AN: 1078726

Other (OTH) AF: 0.0000345 AC: 2 AN: 57984

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72956

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40490

American (AMR) AF: 0.00 AC: 0 AN: 14800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 4936

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67834

Other (OTH) AF: 0.00 AC: 0 AN: 2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.30
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.025
Sift	Uncertain	0.014	D
Sift4G	Benign	0.14	T
Polyphen		0.45	B
Vest4		0.19
MVP		0.25
ClinPred		0.15	T
GERP RS		0.15
PromoterAI		-0.059	Neutral
Varity_R		0.083
gMVP		0.49
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs151265860; hg19: chr20-44144187; COSMIC: COSV54156153;