19-38264766-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021102.4(SPINT2):c.-127C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 999,502 control chromosomes in the GnomAD database, including 30,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4255 hom., cov: 32)
  • Exomes 𝑓: 0.24 (26003 hom.)
• Consequence: SPINT2 NM_021102.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-38264766-C-G is Benign according to our data. Variant chr19-38264766-C-G is described in ClinVar as [Benign]. Clinvar id is 1278110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPINT2	NM_021102.4	c.-127C>G		5_prime_UTR_variant	1/7	ENST00000301244.12
SPINT2	NM_001166103.2	c.-127C>G		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINT2	ENST00000301244.12	c.-127C>G		5_prime_UTR_variant	1/7	1	NM_021102.4	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35462 AN: 152024 Hom.: 4232 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.243 AC: 205736 AN: 847358 Hom.: 26003 Cov.: 11 AF XY: 0.242 AC XY: 103471 AN XY: 427956

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.234 AC: 35534 AN: 152144 Hom.: 4255 Cov.: 32 AF XY: 0.235 AC XY: 17461 AN XY: 74384

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.218

Alfa AF: 0.232 Hom.: 512

Bravo AF: 0.242

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.9
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs1046773; hg19: chr19-38755406;