7-50605298-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001350814.2(GRB10):c.1381G>A(p.Ala461Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,611,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 35)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
GRB10
NM_001350814.2 missense
NM_001350814.2 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 4.73
Genes affected
GRB10 (HGNC:4564): (growth factor receptor bound protein 10) The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRB10 | NM_001350814.2 | c.1381G>A | p.Ala461Thr | missense_variant | 15/19 | ENST00000401949.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRB10 | ENST00000401949.6 | c.1381G>A | p.Ala461Thr | missense_variant | 15/19 | 1 | NM_001350814.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 35
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459540Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726266
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 74392
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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 | Jun 07, 2024 | The c.1381G>A (p.A461T) alteration is located in exon 12 (coding exon 12) of the GRB10 gene. This alteration results from a G to A substitution at nucleotide position 1381, causing the alanine (A) at amino acid position 461 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;D;.;.;.;.;.;.;D;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;.;D;.;D;.;.;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;L;.;.;.;.;.;.;L;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;.;N;N;N;N;.;N;.
REVEL
Uncertain
Sift
Benign
T;T;T;T;.;.;T;T;T;T;.;T;.
Sift4G
Benign
T;T;T;T;.;.;T;T;T;T;.;T;.
Polyphen
0.35, 0.62
.;B;.;.;.;.;.;P;B;.;.;.;P
Vest4
MutPred
0.80
.;Loss of catalytic residue at A461 (P = 0.0436);.;.;.;.;.;.;Loss of catalytic residue at A461 (P = 0.0436);.;.;.;.;
MVP
MPC
0.99
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at