Variant 7-100682230-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001375765.1(GIGYF1):c.2767A>G(p.Met923Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,459,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GIGYF1
NM_001375765.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24221733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1 link	c.2767A>G	p.Met923Val	missense_variant	Exon 25 of 27	ENST00000678049.1	NP_001362694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GIGYF1	ENST00000678049.1 link	c.2767A>G	p.Met923Val	missense_variant	Exon 25 of 27		NM_001375765.1	ENSP00000503354.1	O75420
GIGYF1	ENST00000275732.5 link	c.2767A>G	p.Met923Val	missense_variant	Exon 22 of 24	1		ENSP00000275732.4	O75420
GIGYF1	ENST00000646601.1 link	c.2767A>G	p.Met923Val	missense_variant	Exon 26 of 28			ENSP00000494292.1	O75420

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246232

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459596

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2767A>G (p.M923V) alteration is located in exon 22 (coding exon 22) of the GIGYF1 gene. This alteration results from a A to G substitution at nucleotide position 2767, causing the methionine (M) at amino acid position 923 to be replaced by a valine (V). 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

0.074

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

0.020

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.89

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.21

N;.

REVEL

Benign

0.27

Sift

Uncertain

0.015

D;.

Sift4G

Uncertain

0.040

D;.

Polyphen

0.085

B;B

Vest4

0.61

MutPred

0.34

Loss of disorder (P = 0.2829);Loss of disorder (P = 0.2829);

MVP

0.10

MPC

0.34

ClinPred

0.24

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over