17-48964379-A-G

Position:

• chr17-48964379-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004123.3(GIP):​c.188T>C​(p.Ile63Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GIP NM_004123.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

Genes affected

GIP (HGNC:4270): (gastric inhibitory polypeptide) This gene encodes an incretin hormone and belongs to the glucagon superfamily. The encoded protein is important in maintaining glucose homeostasis as it is a potent stimulator of insulin secretion from pancreatic beta-cells following food ingestion and nutrient absorption. This gene stimulates insulin secretion via its G protein-coupled receptor activation of adenylyl cyclase and other signal transduction pathways. It is a relatively poor inhibitor of gastric acid secretion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIP	NM_004123.3	c.188T>C	p.Ile63Thr	missense_variant	3/6	ENST00000357424.2	NP_004114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIP	ENST00000357424.2	c.188T>C	p.Ile63Thr	missense_variant	3/6	1	NM_004123.3	ENSP00000350005.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Dec 10, 2024

The c.188T>C (p.I63T) alteration is located in exon 3 (coding exon 2) of the GIP gene. This alteration results from a T to C substitution at nucleotide position 188, causing the isoleucine (I) at amino acid position 63 to be replaced by a threonine (T). 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	0.85
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0055	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.17
Sift	Benign	0.17	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.38		Loss of stability (P = 0.0063);
MVP		0.54
MPC		0.21
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.25
gMVP		0.20

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: chr17-47041741;