chr15-40844571-C-T

Variant names:

• chr15-40844571-C-T
• rs1891215139
• NM_003710.4:c.17C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003710.4(SPINT1):​c.17C>T​(p.Thr6Met) 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. 15/22 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. T6R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPINT1 NM_003710.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 0 publications found

Genes affected

SPINT1 (HGNC:11246): (serine peptidase inhibitor, Kunitz type 1) The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008]

SPINT1-AS1 (HGNC:53162): (SPINT1 antisense RNA 1)

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=0.07014477).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003710.4. 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
	SPINT1	NM_003710.4	MANE Select	c.17C>T	p.Thr6Met	missense	Exon 2 of 11	NP_003701.1	O43278-2
	SPINT1	NM_001386873.1		c.17C>T	p.Thr6Met	missense	Exon 2 of 11	NP_001373802.1	O43278-1
	SPINT1	NM_181642.3		c.17C>T	p.Thr6Met	missense	Exon 2 of 11	NP_857593.1	O43278-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT1	ENST00000562057.6	TSL:1 MANE Select	c.17C>T	p.Thr6Met	missense	Exon 2 of 11	ENSP00000457076.1	O43278-2
	SPINT1	ENST00000344051.8	TSL:1	c.17C>T	p.Thr6Met	missense	Exon 2 of 11	ENSP00000342098.4	O43278-1
	SPINT1	ENST00000920945.1		c.17C>T	p.Thr6Met	missense	Exon 2 of 11	ENSP00000591004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	2.7
DANN	Benign	0.90
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.48
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.29
Sift	Benign	0.29	T
Sift4G	Benign	0.20	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.26		Loss of phosphorylation at T6 (P = 0.0165)
MVP		0.65
MPC		0.19
ClinPred		0.054	T
GERP RS		-4.0
PromoterAI		-0.056	Neutral
Varity_R		0.031
gMVP		0.30
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1891215139; hg19: chr15-41136769;