7-100681753-G-A

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

9
9

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]

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/exons MANE Protein UniProt
GIGYF1NM_001375765.1 linkuse as main transcriptc.3074C>T p.Ser1025Phe missense_variant 27/27 ENST00000678049.1 NP_001362694.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GIGYF1ENST00000678049.1 linkuse as main transcriptc.3074C>T p.Ser1025Phe missense_variant 27/27 NM_001375765.1 ENSP00000503354.1 O75420
GIGYF1ENST00000275732.5 linkuse as main transcriptc.3074C>T p.Ser1025Phe missense_variant 24/241 ENSP00000275732.4 O75420
GIGYF1ENST00000646601.1 linkuse as main transcriptc.3074C>T p.Ser1025Phe missense_variant 28/28 ENSP00000494292.1 O75420

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152242
Hom.:
0
Cov.:
33
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:
59
AN:
226364
Hom.:
0
AF XY:
0.000231
AC XY:
28
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.:
0
Cov.:
32
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:
23
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
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.:
0
Bravo
AF:
0.000306
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000280
AC:
34

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 submitterclinical testingAmbry GeneticsOct 06, 2021The 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
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T;T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Uncertain
0.18
D
PrimateAI
Benign
0.44
T
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
T
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.

Other links and lift over

dbSNP: rs201843233; hg19: chr7-100279376; COSMIC: COSV51944802; COSMIC: COSV51944802; API