dbSNP rs17490057: SGIP1:p.Glu112Gln (chr1-66643594-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032291.4(SGIP1):c.334G>C(p.Glu112Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 1,610,632 control chromosomes in the GnomAD database, including 2,920 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 0.042 ( 195 hom., cov: 33)

Exomes 𝑓: 0.057 ( 2725 hom. )

Consequence

SGIP1
NM_032291.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.18

Publications

17 publications found

Variant links:

Genes affected

SGIP1 (HGNC:25412): (SH3GL interacting endocytic adaptor 1) SGIP1 functions as an endocytic protein that affects signaling by receptors in neuronal systems involved in energy homeostasis via its interaction with endophilins (see SH3GL3; MIM 603362) (Trevaskis et al., 2005 [PubMed 15919751] and Uezu et al., 2007 [PubMed 17626015]).[supplied by OMIM, Mar 2008]

SGIP1 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=0.002496928).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGIP1	NM_032291.4 link	c.334G>C	p.Glu112Gln	missense_variant	Exon 7 of 25	ENST00000371037.9	NP_115667.2	Q9BQI5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9 link	c.334G>C	p.Glu112Gln	missense_variant	Exon 7 of 25	1	NM_032291.4	ENSP00000360076.3		Q9BQI5-1

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

6401

AN:

152110

Hom.:

195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00968

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0852

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0625

Gnomad OTH

AF:

0.0368

GnomAD2 exomes

AF:

0.0445

AC:

11029

AN:

247792

AF XY:

0.0441

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0778

Gnomad EAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.0968

Gnomad NFE exome

AF:

0.0605

Gnomad OTH exome

AF:

0.0528

GnomAD4 exome

AF:

0.0567

AC:

82687

AN:

1458404

Hom.:

2725

Cov.:

AF XY:

0.0557

AC XY:

40392

AN XY:

725434

show subpopulations

African (AFR)

AF:

0.00836

AC:

278

AN:

33256

American (AMR)

AF:

0.0172

AC:

760

AN:

44178

Ashkenazi Jewish (ASJ)

AF:

0.0776

AC:

2020

AN:

26046

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39506

South Asian (SAS)

AF:

0.0120

AC:

1028

AN:

85588

European-Finnish (FIN)

AF:

0.0952

AC:

5080

AN:

53362

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0635

AC:

70506

AN:

1110442

Other (OTH)

AF:

0.0488

AC:

2942

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3558

7116

10673

14231

17789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2576

5152

7728

10304

12880

<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:

0.0420

AC:

6400

AN:

152228

Hom.:

195

Cov.:

AF XY:

0.0417

AC XY:

3100

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00965

AC:

401

AN:

41552

American (AMR)

AF:

0.0271

AC:

414

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0835

AC:

290

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0110

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0852

AC:

903

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0625

AC:

4249

AN:

67998

Other (OTH)

AF:

0.0365

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

321

643

964

1286

1607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0574

Hom.:

209

Bravo

AF:

0.0354

TwinsUK

AF:

0.0618

AC:

229

ALSPAC

AF:

0.0693

AC:

267

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.0614

AC:

528

ExAC

AF:

0.0432

AC:

5240

Asia WGS

AF:

0.00404

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;.;T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T;T;T

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;.;.;M

PhyloP100

9.2

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

N;N;D;N

REVEL

Benign

0.19

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Benign

0.067

T;T;T;T

Polyphen

0.94

.;.;.;P

Vest4

0.14

MPC

0.54

ClinPred

0.034

GERP RS

5.3

Varity_R

0.35

gMVP

0.52

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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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