rs1555662027

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5

The NM_001142966.3(GREB1L):​c.4607A>G​(p.His1536Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

GREB1L
NM_001142966.3 missense

Scores

9
5
5

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.95
Variant links:
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 Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GREB1L. . Gene score misZ 5.3659 (greater than the threshold 3.09). Trascript score misZ 5.6738 (greater than threshold 3.09). GenCC has associacion of gene with bilateral renal agenesis, renal hypodysplasia/aplasia 3, renal agenesis, unilateral, hearing loss, autosomal dominant 80.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812
PP5
Variant 18-21508463-A-G is Pathogenic according to our data. Variant chr18-21508463-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 453283.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-21508463-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GREB1LNM_001142966.3 linkuse as main transcriptc.4607A>G p.His1536Arg missense_variant 27/33 ENST00000424526.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GREB1LENST00000424526.7 linkuse as main transcriptc.4607A>G p.His1536Arg missense_variant 27/335 NM_001142966.3 Q9C091-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Renal hypodysplasia/aplasia 3 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 18, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.052
T;.;T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D;D;.
M_CAP
Benign
0.026
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.3
M;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-6.0
D;D;.
REVEL
Uncertain
0.60
Sift
Benign
0.083
T;T;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.86
MutPred
0.66
Loss of catalytic residue at M1538 (P = 0.1152);.;Loss of catalytic residue at M1538 (P = 0.1152);
MVP
0.40
ClinPred
0.96
D
GERP RS
5.8
Varity_R
0.54
gMVP
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1555662027; hg19: chr18-19088424; API