chr7-100682188-C-T

Variant names:

• chr7-100682188-C-T
• NM_001375765.1:c.2809G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375765.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	NM_001375765.1	MANE Select	c.2809G>A	p.Val937Ile	missense	Exon 25 of 27	NP_001362694.1	O75420
	GIGYF1	NM_001375759.1		c.2809G>A	p.Val937Ile	missense	Exon 25 of 26	NP_001362688.1
	GIGYF1	NM_001375760.1		c.2809G>A	p.Val937Ile	missense	Exon 25 of 26	NP_001362689.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	ENST00000678049.1	MANE Select	c.2809G>A	p.Val937Ile	missense	Exon 25 of 27	ENSP00000503354.1	O75420
	GIGYF1	ENST00000275732.5	TSL:1	c.2809G>A	p.Val937Ile	missense	Exon 22 of 24	ENSP00000275732.4	O75420
	GIGYF1	ENST00000893817.1		c.2842G>A	p.Val948Ile	missense	Exon 25 of 27	ENSP00000563876.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Uncertain	-0.094	T
PhyloP100		5.9
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
Vest4		0.53
MutPred		0.15		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
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chr7-100279811;