chr1-66671016-T-C

Position:

• chr1-66671016-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_032291.4(SGIP1):​c.505T>C​(p.Ser169Pro) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGIP1 NM_032291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.95

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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity SGIP1_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGIP1	NM_032291.4	c.505T>C	p.Ser169Pro	missense_variant	10/25	ENST00000371037.9	NP_115667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGIP1	ENST00000371037.9	c.505T>C	p.Ser169Pro	missense_variant	10/25	1	NM_032291.4	ENSP00000360076
	ENST00000502413.2	n.53-4049A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1242638 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 621868

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: 0.00

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

Sep 20, 2023

The c.505T>C (p.S169P) alteration is located in exon 10 (coding exon 10) of the SGIP1 gene. This alteration results from a T to C substitution at nucleotide position 505, causing the serine (S) at amino acid position 169 to be replaced by a proline (P). 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	0.24
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;.;T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.22
Sift	Benign	0.043	D;D;T;T
Sift4G	Benign	0.066	T;T;T;T
Polyphen		0.97	.;.;.;D
Vest4		0.51
MutPred		0.20		.;.;.;Loss of phosphorylation at S169 (P = 0.0023);
MVP		0.44
MPC		0.37
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.60
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr1-67136699;