1-24364647-T-C

Variant names:

• chr1-24364647-T-C
• rs12079868
• NM_001199013.2:c.738-3606A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001199013.2(STPG1):​c.738-3606A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,116 control chromosomes in the GnomAD database, including 2,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (2418 hom., cov: 32)
• Consequence: STPG1 NM_001199013.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.419
• Publications: 0 publications found

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]

GRHL3 Gene-Disease associations (from GenCC):

• van der Woude syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• van der Woude syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-24364647-T-C is Benign according to our data. Variant chr1-24364647-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199013.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STPG1	NM_001199013.2	MANE Select	c.738-3606A>G		intron	N/A	NP_001185942.1	Q5TH74-1
	STPG1	NM_001199012.2		c.738-3606A>G		intron	N/A	NP_001185941.1	Q5TH74-1
	STPG1	NM_178122.5		c.597-3606A>G		intron	N/A	NP_835223.1	Q5TH74-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STPG1	ENST00000337248.9	TSL:5 MANE Select	c.738-3606A>G		intron	N/A	ENSP00000337461.4	Q5TH74-1
	STPG1	ENST00000468303.5	TSL:1	n.4211-3606A>G		intron	N/A
	STPG1	ENST00000374409.5	TSL:2	c.738-3606A>G		intron	N/A	ENSP00000363530.1	Q5TH74-1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18377 AN: 151998 Hom.: 2408 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18413 AN: 152116 Hom.: 2418 Cov.: 32 AF XY: 0.120 AC XY: 8901 AN XY: 74366

African (AFR) AF: 0.327 AC: 13553 AN: 41438

American (AMR) AF: 0.0895 AC: 1369 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3468

East Asian (EAS) AF: 0.0344 AC: 178 AN: 5168

South Asian (SAS) AF: 0.104 AC: 501 AN: 4818

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2188 AN: 68006

Other (OTH) AF: 0.117 AC: 247 AN: 2112

Alfa AF: 0.0934 Hom.: 480

Bravo AF: 0.133

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.77
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12079868; hg19: chr1-24691137;