rs754006408

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_001195010.2(GRHL3):​c.2T>A​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

GRHL3
NM_001195010.2 start_lost

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.17
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 3 CDS bases. Genomic position: 24331549. Lost 0.002 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRHL3NM_198173.3 linkc.140T>A p.Met47Lys missense_variant Exon 2 of 16 ENST00000361548.9 NP_937816.1 Q8TE85-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRHL3ENST00000361548.9 linkc.140T>A p.Met47Lys missense_variant Exon 2 of 16 1 NM_198173.3 ENSP00000354943.5 Q8TE85-5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.63
.;D;.;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D;D;D;D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.72
D;D;D;D;D
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.6
M;M;.;.;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.8
D;D;D;D;D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Uncertain
0.042
D;D;D;D;D
Polyphen
0.44
.;.;.;.;B
Vest4
0.83
MutPred
0.53
Gain of ubiquitination at M47 (P = 0.0185);Gain of ubiquitination at M47 (P = 0.0185);.;.;.;
MVP
0.40
MPC
1.0
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.89
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs754006408; hg19: chr1-24658038; API