20-45512812-C-G

Variant names:

• chr20-45512812-C-G
• rs1176039969
• NM_006652.2:c.109G>C

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.109G>C​(p.Ala37Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A37T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPINT3 NM_006652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• 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=0.14448336).

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.109G>C	p.Ala37Pro	missense	Exon 2 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.109G>C	p.Ala37Pro	missense	Exon 2 of 2	ENSP00000217428.6	P49223
	ENSG00000237464	ENST00000803561.1		n.120-20462C>G		intron	N/A
	ENSG00000237464	ENST00000803562.1		n.127-20462C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.7
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.0070
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.070
Sift	Benign	0.30	T
Sift4G	Benign	0.31	T
Polyphen		0.99	D
Vest4		0.11
MutPred		0.41		Gain of ubiquitination at K42 (P = 0.0539)
MVP		0.19
ClinPred		0.19	T
GERP RS		-0.94
Varity_R		0.26
gMVP		0.69
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1176039969; hg19: chr20-44141452;