7-100681721-A-C

Position:

• chr7-100681721-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_001375765.1(GIGYF1):​c.3106T>G​(p.Ter1036GlyextTer72) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GIGYF1 NM_001375765.1 stop_lost
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.02

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001375765.1 Downstream stopcodon found after 27 codons.
• PP5: Variant 7-100681721-A-C is Pathogenic according to our data. Variant chr7-100681721-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 2430005.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF1	NM_001375765.1	c.3106T>G	p.Ter1036GlyextTer72	stop_lost	27/27	ENST00000678049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF1	ENST00000678049.1	c.3106T>G	p.Ter1036GlyextTer72	stop_lost	27/27		NM_001375765.1	P1
GIGYF1	ENST00000275732.5	c.3106T>G	p.Ter1036GlyextTer72	stop_lost	24/24	1		P1
GIGYF1	ENST00000646601.1	c.3106T>G	p.Ter1036GlyextTer72	stop_lost	28/28			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.92
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.97	D
MutationTaster	Benign	1.0	N
Vest4		0.094
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: chr7-100279344;