Variant 7-100681753-G-A 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.3074C>T(p.Ser1025Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00022 in 1,584,510 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: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

GIGYF1
NM_001375765.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

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:

Genome browser will be placed here

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=0.12665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1 link	c.3074C>T	p.Ser1025Phe	missense_variant	Exon 27 of 27	ENST00000678049.1	NP_001362694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GIGYF1	ENST00000678049.1 link	c.3074C>T	p.Ser1025Phe	missense_variant	Exon 27 of 27		NM_001375765.1	ENSP00000503354.1	O75420
GIGYF1	ENST00000275732.5 link	c.3074C>T	p.Ser1025Phe	missense_variant	Exon 24 of 24	1		ENSP00000275732.4	O75420
GIGYF1	ENST00000646601.1 link	c.3074C>T	p.Ser1025Phe	missense_variant	Exon 28 of 28			ENSP00000494292.1	O75420

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000261

AC:

AN:

226364

Hom.:

AF XY:

0.000231

AC XY:

AN XY:

121418

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000730

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:

0.000322

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.000228

AC:

326

AN:

1432268

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

150

AN XY:

709250

show subpopulations

Gnomad4 AFR exome

AF:

0.0000607

Gnomad4 AMR exome

AF:

0.000914

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.000271

GnomAD4 genome

AF:

0.000151

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000284

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000280

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3074C>T (p.S1025F) alteration is located in exon 24 (coding exon 24) of the GIGYF1 gene. This alteration results from a C to T substitution at nucleotide position 3074, causing the serine (S) at amino acid position 1025 to be replaced by a phenylalanine (F). 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

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.13

T;T

MetaSVM

Uncertain

0.18

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.6

D;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0020

D;.

Polyphen

0.34

B;B

Vest4

0.20

MVP

0.45

MPC

0.74

ClinPred

0.16

GERP RS

5.0

Varity_R

0.35

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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