rs545809

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198174.3(GRHL3):c.1784T>A(p.Met595Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,548,420 control chromosomes in the GnomAD database, including 58,230 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5291 hom., cov: 32)

Exomes 𝑓: 0.27 ( 52939 hom. )

Consequence

GRHL3
NM_198174.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.294

Variant links:

Genes affected

STPG1 (HGNC:28070): (sperm tail PG-rich repeat containing 1) Involved in positive regulation of apoptotic process and positive regulation of mitochondrial membrane permeability involved in apoptotic process. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STPG1 links:

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]

GRHL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016256869).

BP6

Variant 1-24364274-T-A is Benign according to our data. Variant chr1-24364274-T-A is described in ClinVar as [Benign]. Clinvar id is 1164479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STPG1	NM_001199013.2 link	c.738-3233A>T		intron_variant	Intron 7 of 8	ENST00000337248.9	NP_001185942.1	Q5TH74-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STPG1	ENST00000337248.9 link	c.738-3233A>T		intron_variant	Intron 7 of 8	5	NM_001199013.2	ENSP00000337461.4		Q5TH74-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39679

AN:

151960

Hom.:

5281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.292

AC:

42937

AN:

147140

Hom.:

6606

AF XY:

0.298

AC XY:

23594

AN XY:

79248

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.272

AC:

379220

AN:

1396342

Hom.:

52939

Cov.:

AF XY:

0.275

AC XY:

189187

AN XY:

688648

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.261

AC:

39725

AN:

152078

Hom.:

5291

Cov.:

AF XY:

0.263

AC XY:

19519

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.276

Hom.:

4533

Bravo

AF:

0.261

TwinsUK

AF:

0.273

AC:

1011

ALSPAC

AF:

0.274

AC:

1055

ExAC

AF:

0.275

AC:

5754

Asia WGS

AF:

0.359

AC:

1248

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Van der Woude syndrome 2

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.4

DANN

Benign

0.87

DEOGEN2

Benign

0.27

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

REVEL

Benign

0.026

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.096

MPC

0.60

ClinPred

0.023

GERP RS

-1.2

Varity_R

0.64

gMVP

0.46

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over