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GeneBe

19-38264938-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021102.4(SPINT2):c.46C>T(p.Leu16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000561 in 1,536,544 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

SPINT2
NM_021102.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44
Variant links:
Genes affected
SPINT2 (HGNC:11247): (serine peptidase inhibitor, Kunitz type 2) This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-38264938-C-T is Benign according to our data. Variant chr19-38264938-C-T is described in ClinVar as [Benign]. Clinvar id is 1165304.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.44 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00044 (67/152266) while in subpopulation SAS AF= 0.00104 (5/4826). AF 95% confidence interval is 0.000482. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 67 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPINT2NM_021102.4 linkuse as main transcriptc.46C>T p.Leu16= synonymous_variant 1/7 ENST00000301244.12
SPINT2NM_001166103.2 linkuse as main transcriptc.46C>T p.Leu16= synonymous_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPINT2ENST00000301244.12 linkuse as main transcriptc.46C>T p.Leu16= synonymous_variant 1/71 NM_021102.4 P1O43291-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000440
AC:
67
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000780
AC:
108
AN:
138500
Hom.:
1
AF XY:
0.000807
AC XY:
60
AN XY:
74340
show subpopulations
Gnomad AFR exome
AF:
0.000128
Gnomad AMR exome
AF:
0.000244
Gnomad ASJ exome
AF:
0.00361
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00110
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000784
Gnomad OTH exome
AF:
0.00120
GnomAD4 exome
AF:
0.000574
AC:
795
AN:
1384278
Hom.:
1
Cov.:
31
AF XY:
0.000592
AC XY:
404
AN XY:
682940
show subpopulations
Gnomad4 AFR exome
AF:
0.0000635
Gnomad4 AMR exome
AF:
0.000253
Gnomad4 ASJ exome
AF:
0.00362
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00105
Gnomad4 FIN exome
AF:
0.0000267
Gnomad4 NFE exome
AF:
0.000514
Gnomad4 OTH exome
AF:
0.000780
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000440
AC:
67
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.000430
AC XY:
32
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000632
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00105
Hom.:
0
Bravo
AF:
0.000465

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 06, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
12
Dann
Benign
0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs367656580; hg19: chr19-38755578; API