15-40853721-C-T

Variant names:

• chr15-40853721-C-T
• rs17658212
• NM_003710.4:c.753C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003710.4(SPINT1):​c.753C>T​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,614,104 control chromosomes in the GnomAD database, including 2,720 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (171 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2549 hom.)
• Consequence: SPINT1 NM_003710.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

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.753C>T	p.Leu251Leu	synonymous	Exon 5 of 11	NP_003701.1	O43278-2
	SPINT1	NM_001386873.1		c.753C>T	p.Leu251Leu	synonymous	Exon 5 of 11	NP_001373802.1	O43278-1
	SPINT1	NM_181642.3		c.753C>T	p.Leu251Leu	synonymous	Exon 5 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.753C>T	p.Leu251Leu	synonymous	Exon 5 of 11	ENSP00000457076.1	O43278-2
	SPINT1	ENST00000344051.8	TSL:1	c.753C>T	p.Leu251Leu	synonymous	Exon 5 of 11	ENSP00000342098.4	O43278-1
	SPINT1	ENST00000920945.1		c.777C>T	p.Leu259Leu	synonymous	Exon 5 of 11	ENSP00000591004.1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6238 AN: 152218 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0724

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0617

GnomAD2 exomes AF: 0.0418 AC: 10493 AN: 251198 AF XY: 0.0425

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0375

Gnomad ASJ exome AF: 0.0625

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0284

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0535

GnomAD4 exome AF: 0.0548 AC: 80104 AN: 1461768 Hom.: 2549 Cov.: 33 AF XY: 0.0542 AC XY: 39421 AN XY: 727170

African (AFR) AF: 0.00962 AC: 322 AN: 33480

American (AMR) AF: 0.0405 AC: 1812 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 1688 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0153 AC: 1324 AN: 86258

European-Finnish (FIN) AF: 0.0270 AC: 1443 AN: 53396

Middle Eastern (MID) AF: 0.0593 AC: 342 AN: 5768

European-Non Finnish (NFE) AF: 0.0630 AC: 70069 AN: 1111926

Other (OTH) AF: 0.0513 AC: 3100 AN: 60382

GnomAD4 genome AF: 0.0409 AC: 6238 AN: 152336 Hom.: 171 Cov.: 32 AF XY: 0.0388 AC XY: 2892 AN XY: 74496

African (AFR) AF: 0.0121 AC: 502 AN: 41576

American (AMR) AF: 0.0495 AC: 758 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0724 AC: 251 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0130 AC: 63 AN: 4834

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10624

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0617 AC: 4196 AN: 68024

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0552 Hom.: 632

Bravo AF: 0.0427

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.0690

EpiControl AF: 0.0666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.7
DANN	Benign	0.71
PhyloP100		-0.72
PromoterAI		-0.0087	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 13

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

Other links and lift over

dbSNP: rs17658212; hg19: chr15-41145919;