Variant 1-66625876-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032291.4(SGIP1):c.40G>A(p.Gly14Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SGIP1
NM_032291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.67

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGIP1	NM_032291.4 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/25	ENST00000371037.9	NP_115667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/25	1	NM_032291.4	ENSP00000360076		Q9BQI5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250486

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135368

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 SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460076

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.40G>A (p.G14R) alteration is located in exon 2 (coding exon 2) of the SGIP1 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.096

.;.;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.1

M;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

.;.;.;D

Vest4

0.84

MutPred

0.34

Gain of MoRF binding (P = 0.059);Gain of MoRF binding (P = 0.059);Gain of MoRF binding (P = 0.059);Gain of MoRF binding (P = 0.059);

MVP

0.52

MPC

0.62

ClinPred

0.99

GERP RS

5.4

Varity_R

0.57

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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