Variant rs17490057 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SGIP1	NM_032291.4 linkuse as main transcript	c.334G>C	p.Glu112Gln	missense_variant	7/25	ENST00000371037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGIP1	ENST00000371037.9 linkuse as main transcript	c.334G>C	p.Glu112Gln	missense_variant	7/25	1	NM_032291.4		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

GnomAD3 exomes

AF:

0.0445

AC:

11029

AN:

247792

Hom.:

376

AF XY:

0.0441

AC XY:

5901

AN XY:

133916

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 SAS exome

AF:

0.0117

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

Gnomad4 AFR exome

AF:

0.00836

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.0776

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.0952

Gnomad4 NFE exome

AF:

0.0635

Gnomad4 OTH exome

AF:

0.0488

GnomAD4 genome

AF:

0.0420

AC:

6400

AN:

152228

Hom.:

195

Cov.:

AF XY:

0.0417

AC XY:

3100

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00965

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.0852

Gnomad4 NFE

AF:

0.0625

Gnomad4 OTH

AF:

0.0365

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

Dann

Uncertain

1.0

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

MutationTaster

Benign

1.0

D;D;D;D;D

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over