dbSNP rs771414831: SPINK2:p.Ala18Thr (chr4-56821611-C-T) – 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_001271718.2(SPINK2):c.52G>A(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,549,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SPINK2
NM_001271718.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.295

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 29
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

SPINK2 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=0.21428955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271718.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPINK2	NM_001271718.2	MANE Select	c.52G>A	p.Ala18Thr	missense	Exon 1 of 4	NP_001258647.1	D6RI10
SPINK2	NM_001271722.2		c.52G>A	p.Ala18Thr	missense	Exon 1 of 2	NP_001258651.1	A0A087WTA9
SPINK2	NM_001271720.2		c.52G>A	p.Ala18Thr	missense	Exon 1 of 4	NP_001258649.1	D6RC51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPINK2	ENST00000506738.6	TSL:2 MANE Select	c.52G>A	p.Ala18Thr	missense	Exon 1 of 4	ENSP00000425961.1	D6RI10
SPINK2	ENST00000248701.8	TSL:1	c.52G>A	p.Ala18Thr	missense	Exon 1 of 4	ENSP00000248701.4	P20155
SPINK2	ENST00000618802.3	TSL:3	c.52G>A	p.Ala18Thr	missense	Exon 1 of 2	ENSP00000477722.1	A0A087WTA9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000678

AC:

AN:

147404

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1397494

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

689596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31478

American (AMR)

AF:

0.00

AC:

AN:

36216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35820

South Asian (SAS)

AF:

0.00

AC:

AN:

79192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5188

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1079612

Other (OTH)

AF:

0.00

AC:

AN:

57926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2090

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

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000194

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.29

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.72

PhyloP100

0.29

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

REVEL

Benign

0.27

Sift

Benign

0.082

Sift4G

Benign

0.43

Polyphen

0.96

Vest4

0.24

MutPred

0.50

Loss of helix (P = 0.0304)

MVP

0.30

MPC

0.42

ClinPred

0.91

GERP RS

1.9

PromoterAI

0.040

Neutral

(source)

Varity_R

0.077

gMVP

0.35

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over