18-21383555-C-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001142966.3(GREB1L):c.37C>T(p.Arg13Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000215 in 1,394,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as association (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
GREB1L
NM_001142966.3 stop_gained
NM_001142966.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.87
Genes affected
GREB1L (HGNC:31042): (GREB1 like retinoic acid receptor coactivator) Acts upstream of or within kidney development. Predicted to be integral component of membrane. Implicated in autosomal dominant nonsyndromic deafness and renal agenesis. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 71 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GREB1L | NM_001142966.3 | c.37C>T | p.Arg13Ter | stop_gained | 3/33 | ENST00000424526.7 | |
LOC101927521 | XR_001753366.2 | n.245-2880G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GREB1L | ENST00000424526.7 | c.37C>T | p.Arg13Ter | stop_gained | 3/33 | 5 | NM_001142966.3 | ||
ENST00000584611.1 | n.290-2880G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000215 AC: 3AN: 1394100Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1AN XY: 687396
GnomAD4 exome
AF:
AC:
3
AN:
1394100
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
687396
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Alfa
AF:
Hom.:
ClinVar
Significance: association
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Renal agenesis and hypodysplasia Other:1
association, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Nov 02, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at