rs41268753
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_198173.3(GRHL3):c.1361C>T(p.Thr454Met) variant causes a missense change. The variant allele was found at a frequency of 0.0304 in 1,614,014 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 55 hom., cov: 32)
Exomes 𝑓: 0.031 ( 912 hom. )
Consequence
GRHL3
NM_198173.3 missense
NM_198173.3 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 6.00
Genes affected
GRHL3 (HGNC:25839): (grainyhead like transcription factor 3) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0035236776).
BP6
?
Variant 1-24342967-C-T is Benign according to our data. Variant chr1-24342967-C-T is described in ClinVar as [Benign]. Clinvar id is 465245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-24342967-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0224 (3402/152148) while in subpopulation NFE AF= 0.0337 (2290/67998). AF 95% confidence interval is 0.0325. There are 55 homozygotes in gnomad4. There are 1686 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3402 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL3 | NM_198173.3 | c.1361C>T | p.Thr454Met | missense_variant | 11/16 | ENST00000361548.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL3 | ENST00000361548.9 | c.1361C>T | p.Thr454Met | missense_variant | 11/16 | 1 | NM_198173.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0224 AC: 3403AN: 152030Hom.: 56 Cov.: 32
GnomAD3 genomes
?
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3403
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GnomAD3 exomes AF: 0.0228 AC: 5744AN: 251466Hom.: 103 AF XY: 0.0231 AC XY: 3143AN XY: 135912
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GnomAD4 exome AF: 0.0313 AC: 45693AN: 1461866Hom.: 912 Cov.: 32 AF XY: 0.0309 AC XY: 22497AN XY: 727238
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GnomAD4 genome ? AF: 0.0224 AC: 3402AN: 152148Hom.: 55 Cov.: 32 AF XY: 0.0227 AC XY: 1686AN XY: 74374
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127
ALSPAC
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152
ESP6500AA
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27
ESP6500EA
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273
ExAC
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2765
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | This variant is associated with the following publications: (PMID: 27018475, 27018472, 28886269) - |
Van der Woude syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
MPC
1.1
ClinPred
T
GERP RS
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