Genetic Variant NM_178455.3:c.217G>A (chr20-45723981-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178455.3(SPINT4):c.217G>A(p.Gly73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.396 in 1,609,072 control chromosomes in the GnomAD database, including 134,996 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 18001 hom., cov: 31)

Exomes 𝑓: 0.39 ( 116995 hom. )

Consequence

SPINT4
NM_178455.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.93

Publications

41 publications found

Variant links:

Genes affected

SPINT4 (HGNC:16130): (serine peptidase inhibitor, Kunitz type 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPINT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9414892E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT4	NM_178455.3 link	c.217G>A	p.Gly73Ser	missense_variant	Exon 2 of 3	ENST00000279058.4	NP_848550.1	Q6UDR6A0A384P5R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT4	ENST00000279058.4 link	c.217G>A	p.Gly73Ser	missense_variant	Exon 2 of 3	1	NM_178455.3	ENSP00000279058.3		Q6UDR6

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70430

AN:

151820

Hom.:

17980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.472

GnomAD2 exomes

AF:

0.416

AC:

102894

AN:

247122

AF XY:

0.423

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.389

AC:

566767

AN:

1457134

Hom.:

116995

Cov.:

AF XY:

0.395

AC XY:

285950

AN XY:

724840

show subpopulations

African (AFR)

AF:

0.686

AC:

22627

AN:

32988

American (AMR)

AF:

0.286

AC:

12485

AN:

43686

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

14234

AN:

26026

East Asian (EAS)

AF:

0.461

AC:

18222

AN:

39548

South Asian (SAS)

AF:

0.547

AC:

46609

AN:

85180

European-Finnish (FIN)

AF:

0.386

AC:

20598

AN:

53344

Middle Eastern (MID)

AF:

0.526

AC:

3022

AN:

5748

European-Non Finnish (NFE)

AF:

0.363

AC:

403073

AN:

1110434

Other (OTH)

AF:

0.430

AC:

25897

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

17652

35305

52957

70610

88262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12986

25972

38958

51944

64930

<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:

0.464

AC:

70489

AN:

151938

Hom.:

18001

Cov.:

AF XY:

0.465

AC XY:

34548

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.673

AC:

27915

AN:

41456

American (AMR)

AF:

0.348

AC:

5304

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1855

AN:

3472

East Asian (EAS)

AF:

0.490

AC:

2534

AN:

5174

South Asian (SAS)

AF:

0.549

AC:

2642

AN:

4812

European-Finnish (FIN)

AF:

0.391

AC:

4119

AN:

10534

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24756

AN:

67920

Other (OTH)

AF:

0.470

AC:

989

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1801

3602

5403

7204

9005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.402

Hom.:

54272

Bravo

AF:

0.468

TwinsUK

AF:

0.374

AC:

1385

ALSPAC

AF:

0.363

AC:

1400

ESP6500AA

AF:

0.641

AC:

2825

ESP6500EA

AF:

0.375

AC:

3223

ExAC

AF:

0.426

AC:

51725

Asia WGS

AF:

0.495

AC:

1723

AN:

3478

EpiCase

AF:

0.383

EpiControl

AF:

0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

MetaRNN

Benign

0.00029

MetaSVM

Benign

-0.88

PhyloP100

3.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MPC

0.87

ClinPred

0.037

GERP RS

4.5

Varity_R

0.89

gMVP

0.95

Mutation Taster

=82/18

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over