rs977334887

Variant names:

• chr20-45515556-T-C
• NM_006652.2:c.53A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-45515556-T-C
• chr20-45515556-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006652.2(SPINT3):​c.53A>G​(p.Glu18Gly) 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 1,399,026 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: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SPINT3 NM_006652.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29275918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT3	NM_006652.2	c.53A>G	p.Glu18Gly	missense_variant	Exon 1 of 2	ENST00000217428.7	NP_006643.1
LOC107987282	XR_001754641.3	n.100-17718T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT3	ENST00000217428.7	c.53A>G	p.Glu18Gly	missense_variant	Exon 1 of 2	1	NM_006652.2	ENSP00000217428.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399026 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

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 Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.14	T
Sift4G	Benign	0.095	T
Polyphen		0.98	D
Vest4		0.36
MutPred		0.51		Gain of loop (P = 0.002);
MVP		0.20
ClinPred		0.13	T
GERP RS		0.91
Varity_R		0.078
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-44144196;