rs1176039969

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-45512812-C-A
• chr20-45512812-C-G
• chr20-45512812-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.109G>T​(p.Ala37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,326 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. 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SPINT3 NM_006652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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=0.050094336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT3	NM_006652.2	c.109G>T	p.Ala37Ser	missense_variant	Exon 2 of 2	ENST00000217428.7	NP_006643.1
LOC107987282	XR_001754641.3	n.100-20462C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT3	ENST00000217428.7	c.109G>T	p.Ala37Ser	missense_variant	Exon 2 of 2	1	NM_006652.2	ENSP00000217428.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000639 AC: 1 AN: 156420 Hom.: 0 AF XY: 0.0000121 AC XY: 1 AN XY: 82820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399326 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690162

Gnomad4 AFR exome AF: 0.00

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.014
DANN	Benign	0.15
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.015
Sift	Benign	0.86	T
Sift4G	Benign	0.87	T
Polyphen		0.13	B
Vest4		0.032
MutPred		0.41		Gain of ubiquitination at K42 (P = 0.0651);
MVP		0.12
ClinPred		0.10	T
GERP RS		-0.94
Varity_R		0.036
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 32

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1176039969; hg19: chr20-44141452;