Variant 4-56821545-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001271718.2(SPINK2):c.118A>G(p.Thr40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 1,545,832 control chromosomes in the GnomAD database, including 13,190 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 5376 hom., cov: 33)

Exomes 𝑓: 0.075 ( 7814 hom. )

Consequence

SPINK2
NM_001271718.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0700

Variant links:

Genes affected

SPINK2 (HGNC:11245): (serine peptidase inhibitor Kazal type 2) This gene encodes a member of the family of serine protease inhibitors of the Kazal type (SPINK). The encoded protein acts as a trypsin and acrosin inhibitor in the genital tract and is localized in the spermatozoa. The protein has been associated with the progression of lymphomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SPINK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2730231E-4).

BP6

Variant 4-56821545-T-C is Benign according to our data. Variant chr4-56821545-T-C is described in ClinVar as [Benign]. Clinvar id is 3058909.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK2	NM_001271718.2 linkuse as main transcript	c.118A>G	p.Thr40Ala	missense_variant	1/4	ENST00000506738.6	NP_001258647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK2	ENST00000506738.6 linkuse as main transcript	c.118A>G	p.Thr40Ala	missense_variant	1/4	2	NM_001271718.2	ENSP00000425961	A2

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29052

AN:

151846

Hom.:

5359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.0847

Gnomad SAS

AF:

0.0328

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.0580

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.115

AC:

16051

AN:

139724

Hom.:

1865

AF XY:

0.0995

AC XY:

7529

AN XY:

75668

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.0966

Gnomad EAS exome

AF:

0.0873

Gnomad SAS exome

AF:

0.0293

Gnomad FIN exome

AF:

0.0604

Gnomad NFE exome

AF:

0.0589

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0746

AC:

103941

AN:

1393872

Hom.:

7814

Cov.:

AF XY:

0.0712

AC XY:

48924

AN XY:

687500

show subpopulations

Gnomad4 AFR exome

AF:

0.489

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.0951

Gnomad4 EAS exome

AF:

0.0784

Gnomad4 SAS exome

AF:

0.0293

Gnomad4 FIN exome

AF:

0.0584

Gnomad4 NFE exome

AF:

0.0585

Gnomad4 OTH exome

AF:

0.0962

GnomAD4 genome

AF:

0.191

AC:

29096

AN:

151960

Hom.:

5376

Cov.:

AF XY:

0.188

AC XY:

13957

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.476

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.0878

Gnomad4 EAS

AF:

0.0843

Gnomad4 SAS

AF:

0.0318

Gnomad4 FIN

AF:

0.0706

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.118

Hom.:

482

Bravo

AF:

0.223

TwinsUK

AF:

0.0485

AC:

180

ALSPAC

AF:

0.0586

AC:

226

ExAC

AF:

0.0604

AC:

3528

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SPINK2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

DANN

Benign

0.60

DEOGEN2

Benign

0.0038

.;T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00093

LIST_S2

Benign

0.27

T;T;T;T;T

MetaRNN

Benign

0.00023

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.19

N;.;.;N;.

REVEL

Benign

0.10

Sift

Benign

1.0

T;.;.;T;.

Sift4G

Benign

0.63

T;T;T;T;T

Vest4

0.066

ClinPred

0.0033

GERP RS

-0.79

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over