rs17658212

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-40853721-C-A
• chr15-40853721-C-G
• chr15-40853721-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003710.4(SPINT1):​c.753C>A​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPINT1 NM_003710.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.723 with no splicing effect.

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461774 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.36
DANN	Benign	0.71
PhyloP100		-0.72
PromoterAI		-0.022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs17658212; hg19: chr15-41145919;