20-45515547-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006652.2(SPINT3):​c.62C>A​(p.Ser21*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SPINT3 NM_006652.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT3	NM_006652.2	c.62C>A	p.Ser21*	stop_gained	Exon 1 of 2	ENST00000217428.7	NP_006643.1
LOC107987282	XR_001754641.3	n.100-17727G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT3	ENST00000217428.7	c.62C>A	p.Ser21*	stop_gained	Exon 1 of 2	1	NM_006652.2	ENSP00000217428.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398926 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689976

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Benign	0.96
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.10	N
Vest4		0.054
GERP RS		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44144187;