1-66643652-A-G

Variant names:

• chr1-66643652-A-G
• rs7526812
• NM_032291.4:c.392A>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 34 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=0.0038033724).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	NM_032291.4	MANE Select	c.392A>G	p.Lys131Arg	missense	Exon 7 of 25	NP_115667.2
	SGIP1	NM_001350217.2		c.404A>G	p.Lys135Arg	missense	Exon 7 of 25	NP_001337146.1
	SGIP1	NM_001376534.1		c.392A>G	p.Lys131Arg	missense	Exon 8 of 26	NP_001363463.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGIP1	ENST00000371037.9	TSL:1 MANE Select	c.392A>G	p.Lys131Arg	missense	Exon 7 of 25	ENSP00000360076.3
	SGIP1	ENST00000371039.5	TSL:1	c.320A>G	p.Lys107Arg	missense	Exon 7 of 22	ENSP00000360078.1
	SGIP1	ENST00000237247.10	TSL:5	c.404A>G	p.Lys135Arg	missense	Exon 8 of 27	ENSP00000237247.6

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

GnomAD2 exomes AF: 0.211 AC: 52435 AN: 248330 AF XY: 0.202

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 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

African (AFR) AF: 0.382 AC: 12707 AN: 33268

American (AMR) AF: 0.316 AC: 13925 AN: 44030

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4463 AN: 26080

East Asian (EAS) AF: 0.275 AC: 10890 AN: 39614

South Asian (SAS) AF: 0.226 AC: 19297 AN: 85468

European-Finnish (FIN) AF: 0.144 AC: 7686 AN: 53386

Middle Eastern (MID) AF: 0.180 AC: 1035 AN: 5752

European-Non Finnish (NFE) AF: 0.157 AC: 174398 AN: 1111044

Other (OTH) AF: 0.189 AC: 11420 AN: 60306

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

African (AFR) AF: 0.377 AC: 15662 AN: 41492

American (AMR) AF: 0.242 AC: 3702 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1412 AN: 5166

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4822

European-Finnish (FIN) AF: 0.155 AC: 1639 AN: 10606

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10805 AN: 67990

Other (OTH) AF: 0.194 AC: 411 AN: 2116

Alfa AF: 0.189 Hom.: 10772

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 v4.9

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
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		2.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.068
Sift	Benign	0.21	T
Sift4G	Benign	0.58	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
Mutation Taster		=93/7	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: rs7526812; hg19: chr1-67109335; COSMIC: COSV52764896;