7-100682188-C-T

Position:

• chr7-100682188-C-T

Variant summary

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

The NM_001375765.1(GIGYF1):​c.2809G>A​(p.Val937Ile) 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: 33)
• Consequence: GIGYF1 NM_001375765.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86

Genes affected

GIGYF1 (HGNC:9126): (GRB10 interacting GYF protein 1) This gene encodes a member of the gyf family of adaptor proteins. The encoded protein contains a gyf protein interaction domain. It binds growth factor receptor bound 10, another adaptor protein that binds activated insulin-like growth factor 1 and insulin receptors and regulates receptor signaling. [provided by RefSeq, Apr 2017]

GIGYF1 (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	Protein	UniProt
GIGYF1	NM_001375765.1	c.2809G>A	p.Val937Ile	missense_variant	25/27	ENST00000678049.1	NP_001362694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIGYF1	ENST00000678049.1	c.2809G>A	p.Val937Ile	missense_variant	25/27		NM_001375765.1	ENSP00000503354.1
GIGYF1	ENST00000275732.5	c.2809G>A	p.Val937Ile	missense_variant	22/24	1		ENSP00000275732.4
GIGYF1	ENST00000646601.1	c.2809G>A	p.Val937Ile	missense_variant	26/28			ENSP00000494292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 11, 2023

The c.2809G>A (p.V937I) alteration is located in exon 22 (coding exon 22) of the GIGYF1 gene. This alteration results from a G to A substitution at nucleotide position 2809, causing the valine (V) at amino acid position 937 to be replaced by an isoleucine (I). 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	0.22
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	-0.094	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.77	N;.
REVEL	Benign	0.25
Sift	Benign	0.070	T;.
Sift4G	Benign	0.15	T;.
Polyphen		0.99	D;D
Vest4		0.53
MutPred		0.15		Gain of phosphorylation at Y940 (P = 0.1656);Gain of phosphorylation at Y940 (P = 0.1656);
MVP		0.35
MPC		0.67
ClinPred		0.86	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.69

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: chr7-100279811;