Genetic Variant GIGYF1:p.Met923Leu (chr7-100682230-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001375765.1(GIGYF1):c.2767A>C(p.Met923Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,611,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GIGYF1
NM_001375765.1 missense

Scores

Clinical Significance

Not reported in ClinVar

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=0.2553375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1 link	c.2767A>C	p.Met923Leu	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>C	p.Met923Leu	missense_variant	Exon 25 of 27		NM_001375765.1	ENSP00000503354.1	O75420
GIGYF1	ENST00000275732.5 link	c.2767A>C	p.Met923Leu	missense_variant	Exon 22 of 24	1		ENSP00000275732.4	O75420
GIGYF1	ENST00000646601.1 link	c.2767A>C	p.Met923Leu	missense_variant	Exon 26 of 28			ENSP00000494292.1	O75420

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459596

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.080

T;T

Eigen

Benign

0.010

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.36

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.021

D;.

Sift4G

Uncertain

0.039

D;.

Polyphen

0.037

B;B

Vest4

0.58

MutPred

0.38

Gain of catalytic residue at M923 (P = 0.2538);Gain of catalytic residue at M923 (P = 0.2538);

MVP

0.13

MPC

0.32

ClinPred

0.74

GERP RS

5.1

Varity_R

0.30

gMVP

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over