rs7526812

chr1-66643652-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032291.4(SGIP1):c.392A>G(p.Lys131Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,611,088 control chromosomes in the GnomAD database, including 29,263 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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 0.23 (4878 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24385 hom.)
• Consequence: SGIP1 NM_032291.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038033724).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGIP1	NM_032291.4	c.392A>G	p.Lys131Arg	missense_variant	7/25	ENST00000371037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGIP1	ENST00000371037.9	c.392A>G	p.Lys131Arg	missense_variant	7/25	1	NM_032291.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35482 AN: 152022 Hom.: 4862 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.194

GnomAD3 exomes AF: 0.211 AC: 52435 AN: 248330 Hom.: 6457 AF XY: 0.202 AC XY: 27109 AN XY: 134128

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.268

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.175 AC: 255821 AN: 1458948 Hom.: 24385 Cov.: 32 AF XY: 0.175 AC XY: 127083 AN XY: 725640

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.234 AC: 35532 AN: 152140 Hom.: 4878 Cov.: 32 AF XY: 0.234 AC XY: 17425 AN XY: 74360

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.194

Alfa AF: 0.175 Hom.: 5549

Bravo AF: 0.245

TwinsUK AF: 0.161 AC: 598

ALSPAC AF: 0.159 AC: 613

ESP6500AA AF: 0.366 AC: 1612

ESP6500EA AF: 0.151 AC: 1297

ExAC AF: 0.214 AC: 26020

Asia WGS AF: 0.255 AC: 887 AN: 3476

EpiCase AF: 0.160

EpiControl AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Benign	-0.11
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D
MetaRNN	Benign	0.0038	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.86	N;N;N;N
REVEL	Benign	0.068
Sift	Benign	0.21	T;T;T;T
Sift4G	Benign	0.58	T;T;T;T
Polyphen		0.0060	.;.;.;B
Vest4		0.015
MPC		0.48
ClinPred		0.017	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.32

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

Other links and lift over

dbSNP: rs7526812; hg19: chr1-67109335; COSMIC: COSV52764896;