1-24364404-C-T

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

2

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]
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 (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
STPG1NM_001199013.2 linkc.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
STPG1ENST00000337248.9 linkc.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.:
33
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.:
31
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.:
33
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.:
47
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.

Other links and lift over

dbSNP: rs74060321; hg19: chr1-24690894; API