Genetic Variant NM_003710.4:c.124C>A (chr15-40844678-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003710.4(SPINT1):c.124C>A(p.Pro42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P42S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SPINT1
NM_003710.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.592

Publications

0 publications found

Variant links:

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 links:

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

SPINT1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.0962418).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPINT1	NM_003710.4	MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 2 of 11	NP_003701.1	O43278-2
SPINT1	NM_001386873.1		c.124C>A	p.Pro42Thr	missense	Exon 2 of 11	NP_001373802.1	O43278-1
SPINT1	NM_181642.3		c.124C>A	p.Pro42Thr	missense	Exon 2 of 11	NP_857593.1	O43278-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPINT1	ENST00000562057.6	TSL:1 MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 2 of 11	ENSP00000457076.1	O43278-2
SPINT1	ENST00000344051.8	TSL:1	c.124C>A	p.Pro42Thr	missense	Exon 2 of 11	ENSP00000342098.4	O43278-1
SPINT1	ENST00000920945.1		c.124C>A	p.Pro42Thr	missense	Exon 2 of 11	ENSP00000591004.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.00

AC:

AN:

44002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25796

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.00

AC:

AN:

85602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108608

Other (OTH)

AF:

0.00

AC:

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

1.4

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.72

M_CAP

Benign

0.068

MetaRNN

Benign

0.096

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

2.0

PhyloP100

-0.59

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.79

REVEL

Benign

0.25

Sift

Benign

0.059

Sift4G

Uncertain

0.060

Polyphen

0.0040

Vest4

0.22

MutPred

0.24

Loss of catalytic residue at P41 (P = 0.0264)

MVP

0.67

MPC

0.35

ClinPred

0.034

GERP RS

-2.0

PromoterAI

-0.0027

Neutral

(source)

Varity_R

0.039

gMVP

0.43

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over