chr1-66677027-T-G

Position:

• chr1-66677027-T-G

Variant summary

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

The NM_032291.4(SGIP1):​c.670T>G​(p.Trp224Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGIP1 NM_032291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.36

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]

(HGNC:):

ACMG classification

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	UniProt
SGIP1	NM_032291.4	c.670T>G	p.Trp224Gly	missense_variant	13/25	ENST00000371037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGIP1	ENST00000371037.9	c.670T>G	p.Trp224Gly	missense_variant	13/25	1	NM_032291.4
	ENST00000502413.2	n.1A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.670T>G (p.W224G) alteration is located in exon 13 (coding exon 13) of the SGIP1 gene. This alteration results from a T to G substitution at nucleotide position 670, causing the tryptophan (W) at amino acid position 224 to be replaced by a glycine (G). 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	0.57
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	.;.;T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.3	D;D;D;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.97	.;.;.;D
Vest4		0.75
MutPred		0.30		.;.;.;Gain of relative solvent accessibility (P = 0.0098);
MVP		0.12
MPC		0.72
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.88
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.36		Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67142710;