Variant 7-100682166-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001375765.1(GIGYF1):c.2831G>C(p.Cys944Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GIGYF1
NM_001375765.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF1	NM_001375765.1 linkuse as main transcript	c.2831G>C	p.Cys944Ser	missense_variant	25/27	ENST00000678049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GIGYF1	ENST00000678049.1 linkuse as main transcript	c.2831G>C	p.Cys944Ser	missense_variant	25/27		NM_001375765.1	P1
GIGYF1	ENST00000275732.5 linkuse as main transcript	c.2831G>C	p.Cys944Ser	missense_variant	22/24	1		P1
GIGYF1	ENST00000646601.1 linkuse as main transcript	c.2831G>C	p.Cys944Ser	missense_variant	26/28			P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250698

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.2831G>C (p.C944S) alteration is located in exon 22 (coding exon 22) of the GIGYF1 gene. This alteration results from a G to C substitution at nucleotide position 2831, causing the cysteine (C) at amino acid position 944 to be replaced by a serine (S). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.13

Sift

Uncertain

0.025

D;.

Sift4G

Benign

0.11

T;.

Polyphen

0.92

P;P

Vest4

0.69

MutPred

0.53

Gain of disorder (P = 0.0129);Gain of disorder (P = 0.0129);

MVP

0.12

MPC

0.78

ClinPred

0.72

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.50

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

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