chr1-66677090-A-G

Position:

• chr1-66677090-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032291.4(SGIP1):​c.733A>G​(p.Thr245Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SGIP1 NM_032291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.55

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGIP1	NM_032291.4	c.733A>G	p.Thr245Ala	missense_variant	13/25	ENST00000371037.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGIP1	ENST00000371037.9	c.733A>G	p.Thr245Ala	missense_variant	13/25	1	NM_032291.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461316 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726990

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

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

Jul 12, 2023

The c.733A>G (p.T245A) alteration is located in exon 13 (coding exon 13) of the SGIP1 gene. This alteration results from a A to G substitution at nucleotide position 733, causing the threonine (T) at amino acid position 245 to be replaced by an alanine (A). 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	Benign	0.070
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	.;.;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	.;.;.;L
MutationTaster	Benign	0.93	D;N;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.047	D;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.088	.;.;.;B
Vest4		0.49
MutPred		0.12		.;.;.;Loss of glycosylation at T245 (P = 0.0029);
MVP		0.093
MPC		0.13
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67142773;