Genetic Variant GREB1L:p.Arg13Gly (chr18-21383555-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001142966.3(GREB1L):c.37C>G(p.Arg13Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,394,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GREB1L
NM_001142966.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.87

Publications

0 publications found

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]

GREB1L Gene-Disease associations (from GenCC):

renal hypodysplasia/aplasia 3
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
renal agenesis, unilateral
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
bilateral renal agenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal dominant 80
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GREB1L links:

GREB1L-AS1 (HGNC:58310):

GREB1L-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31548935).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142966.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GREB1L	NM_001142966.3	MANE Select	c.37C>G	p.Arg13Gly	missense	Exon 3 of 33	NP_001136438.1	Q9C091-1
GREB1L	NM_001410867.1		c.37C>G	p.Arg13Gly	missense	Exon 3 of 34	NP_001397796.1	J3QQW0
GREB1L	NM_001410868.1		c.37C>G	p.Arg13Gly	missense	Exon 3 of 32	NP_001397797.1	Q9C091-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GREB1L	ENST00000424526.7	TSL:5 MANE Select	c.37C>G	p.Arg13Gly	missense	Exon 3 of 33	ENSP00000412060.1	Q9C091-1
GREB1L	ENST00000578368.5	TSL:1	n.142C>G		non_coding_transcript_exon	Exon 2 of 15
GREB1L	ENST00000584446.5	TSL:1	n.308C>G		non_coding_transcript_exon	Exon 3 of 15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000664

AC:

AN:

150662

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394104

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31262

American (AMR)

AF:

0.00

AC:

AN:

34454

Ashkenazi Jewish (ASJ)

AF:

0.0000797

AC:

AN:

25094

East Asian (EAS)

AF:

0.00

AC:

AN:

35498

South Asian (SAS)

AF:

0.00

AC:

AN:

77678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077330

Other (OTH)

AF:

0.00

AC:

AN:

57834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

ExAC

AF:

0.0000401

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.021

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

PhyloP100

5.9

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.39

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.61

MutPred

0.34

Loss of stability (P = 0.0241)

MVP

0.26

ClinPred

0.98

GERP RS

4.5

Varity_R

0.45

gMVP

0.65

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over