rs17490057

Variant names:

• chr1-66643594-G-C
• rs17490057
• NM_032291.4:c.334G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.18
• Publications: 17 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	NM_032291.4	MANE Select	c.334G>C	p.Glu112Gln	missense	Exon 7 of 25	NP_115667.2	Q9BQI5-1
	SGIP1	NM_001350217.2		c.346G>C	p.Glu116Gln	missense	Exon 7 of 25	NP_001337146.1	Q9BQI5-2
	SGIP1	NM_001376534.1		c.334G>C	p.Glu112Gln	missense	Exon 8 of 26	NP_001363463.1	Q9BQI5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	ENST00000371037.9	TSL:1 MANE Select	c.334G>C	p.Glu112Gln	missense	Exon 7 of 25	ENSP00000360076.3	Q9BQI5-1
	SGIP1	ENST00000371039.5	TSL:1	c.262G>C	p.Glu88Gln	missense	Exon 7 of 22	ENSP00000360078.1	Q9BQI5-5
	SGIP1	ENST00000237247.10	TSL:5	c.346G>C	p.Glu116Gln	missense	Exon 8 of 27	ENSP00000237247.6	Q9BQI5-3

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6401 AN: 152110 Hom.: 195 Cov.: 33

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

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.: 30 AF XY: 0.0557 AC XY: 40392 AN XY: 725434

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: 1 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: 72 AN: 5754

European-Non Finnish (NFE) AF: 0.0635 AC: 70506 AN: 1110442

Other (OTH) AF: 0.0488 AC: 2942 AN: 60272

GnomAD4 genome AF: 0.0420 AC: 6400 AN: 152228 Hom.: 195 Cov.: 33 AF XY: 0.0417 AC XY: 3100 AN XY: 74420

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: 0 AN: 5188

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4818

European-Finnish (FIN) AF: 0.0852 AC: 903 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4249 AN: 67998

Other (OTH) AF: 0.0365 AC: 77 AN: 2112

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: 50

ESP6500EA AF: 0.0614 AC: 528

ExAC AF: 0.0432 AC: 5240

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		9.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.067	T
Polyphen		0.94	P
Vest4		0.14
MPC		0.54
ClinPred		0.034	T
GERP RS		5.3
Varity_R		0.35
gMVP		0.52
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17490057; hg19: chr1-67109277; COSMIC: COSV106358417;