Genetic Variant STPG1:c.738-3363G>A (chr1-24364404-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_198174.3(GRHL3):c.*33C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,506,808 control chromosomes in the GnomAD database, including 1,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 596 hom., cov: 33)

Exomes 𝑓: 0.030 ( 1248 hom. )

Consequence

GRHL3
NM_198174.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.47

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:

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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 (BayesDel_noAF=-0.9).

BP6

Variant 1-24364404-C-T is Benign according to our data. Variant chr1-24364404-C-T is described in ClinVar as [Benign]. Clinvar id is 1264843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STPG1	NM_001199013.2 link	c.738-3363G>A		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.738-3363G>A		intron_variant	Intron 7 of 8	5	NM_001199013.2	ENSP00000337461.4		Q5TH74-1

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9668

AN:

152168

Hom.:

591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0554

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.0344

Gnomad SAS

AF:

0.0978

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0598

GnomAD3 exomes

AF:

0.0451

AC:

4909

AN:

108922

Hom.:

220

AF XY:

0.0482

AC XY:

2728

AN XY:

56546

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.0421

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0304

AC:

41191

AN:

1354524

Hom.:

1248

Cov.:

AF XY:

0.0320

AC XY:

21258

AN XY:

663574

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0344

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0254

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0174

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0395

GnomAD4 genome

AF:

0.0636

AC:

9687

AN:

152284

Hom.:

596

Cov.:

AF XY:

0.0646

AC XY:

4811

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.0553

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.0345

Gnomad4 SAS

AF:

0.0982

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.0217

Gnomad4 OTH

AF:

0.0667

Alfa

AF:

0.0381

Hom.:

Bravo

AF:

0.0682

Asia WGS

AF:

0.120

AC:

415

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

DANN

Benign

0.49

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