rs770962467
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_024915.4(GRHL2):c.1081G>A(p.Val361Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000549 in 1,457,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
GRHL2
NM_024915.4 missense
NM_024915.4 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 5.70
Genes affected
GRHL2 (HGNC:2799): (grainyhead like transcription factor 2) The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL2 | NM_024915.4 | c.1081G>A | p.Val361Met | missense_variant | 8/16 | ENST00000646743.1 | |
GRHL2 | NM_001330593.2 | c.1033G>A | p.Val345Met | missense_variant | 8/16 | ||
GRHL2 | XM_011517306.4 | c.1033G>A | p.Val345Met | missense_variant | 8/16 | ||
GRHL2 | XM_011517307.4 | c.1081G>A | p.Val361Met | missense_variant | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL2 | ENST00000646743.1 | c.1081G>A | p.Val361Met | missense_variant | 8/16 | NM_024915.4 | P1 | ||
GRHL2 | ENST00000395927.1 | c.1033G>A | p.Val345Met | missense_variant | 8/16 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251314Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135834
GnomAD3 exomes
AF:
AC:
2
AN:
251314
Hom.:
AF XY:
AC XY:
1
AN XY:
135834
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1457222Hom.: 0 Cov.: 29 AF XY: 0.00000414 AC XY: 3AN XY: 725310
GnomAD4 exome
AF:
AC:
8
AN:
1457222
Hom.:
Cov.:
29
AF XY:
AC XY:
3
AN XY:
725310
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
Bravo
AF:
ExAC
?
AF:
AC:
3
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 | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 28, 2017 | The p.Val361Met variant in GRHL2 has not been previously reported in individuals with hearing loss, but has been identified in 3/126630 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs770962467). Although this variant has been seen in the general population, it s frequency is not high enough to rule out a pathogenic role. Computational pred iction tools and conservation analysis suggest the variant may impact the protei n, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val361Met variant is uncertain. A CMG/AMP Criteria applied: PM2, PP3. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;.;D
Polyphen
D;D;.
Vest4
MutPred
Gain of ubiquitination at K366 (P = 0.1162);Gain of ubiquitination at K366 (P = 0.1162);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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