rs371429401

Variant names:

• chr20-45515550-C-A
• rs371429401
• NM_006652.2:c.59G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-45515550-C-A
• chr20-45515550-C-G
• chr20-45515550-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006652.2(SPINT3):​c.59G>T​(p.Arg20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,549,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SPINT3 NM_006652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.18

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048309624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT3	NM_006652.2	c.59G>T	p.Arg20Leu	missense_variant	Exon 1 of 2	ENST00000217428.7	NP_006643.1
LOC107987282	XR_001754641.3	n.100-17724C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT3	ENST00000217428.7	c.59G>T	p.Arg20Leu	missense_variant	Exon 1 of 2	1	NM_006652.2	ENSP00000217428.6

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151412 Hom.: 0 Cov.: 32

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: 7.15e-7 AC: 1 AN: 1397746 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689338

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151412 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73864

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.099
DANN	Benign	0.90
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.025
Sift	Benign	0.71	T
Sift4G	Benign	1.0	T
Polyphen		0.072	B
Vest4		0.12
MutPred		0.52		Loss of disorder (P = 0.1963);
MVP		0.067
ClinPred		0.048	T
GERP RS		-6.6
Varity_R		0.033
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs371429401; hg19: chr20-44144190;