Genetic Variant NM_001199013.2:c.738-3363G>A (chr1-24364404-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001199013.2(STPG1):c.738-3363G>A variant causes a intron 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

STPG1
NM_001199013.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.47

Publications

5 publications found

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 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

GRHL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STPG1	NM_001199013.2	MANE Select	c.738-3363G>A	intron	N/A	NP_001185942.1	Q5TH74-1
GRHL3	NM_198174.3		c.*33C>T	3_prime_UTR	Exon 16 of 16	NP_937817.3
STPG1	NM_001199012.2		c.738-3363G>A	intron	N/A	NP_001185941.1	Q5TH74-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STPG1	ENST00000337248.9	TSL:5 MANE Select	c.738-3363G>A	intron	N/A	ENSP00000337461.4	Q5TH74-1
STPG1	ENST00000468303.5	TSL:1	n.4211-3363G>A	intron	N/A
GRHL3	ENST00000350501.9	TSL:2	c.*33C>T	3_prime_UTR	Exon 16 of 16	ENSP00000288955.5	Q8TE85-1

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

GnomAD2 exomes

AF:

0.0451

AC:

4909

AN:

108922

AF XY:

0.0482

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 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

African (AFR)

AF:

0.166

AC:

5091

AN:

30614

American (AMR)

AF:

0.0344

AC:

1079

AN:

31326

Ashkenazi Jewish (ASJ)

AF:

0.0158

AC:

351

AN:

22162

East Asian (EAS)

AF:

0.0254

AC:

876

AN:

34522

South Asian (SAS)

AF:

0.105

AC:

7345

AN:

69854

European-Finnish (FIN)

AF:

0.0174

AC:

810

AN:

46586

Middle Eastern (MID)

AF:

0.0459

AC:

252

AN:

5494

European-Non Finnish (NFE)

AF:

0.0219

AC:

23162

AN:

1057626

Other (OTH)

AF:

0.0395

AC:

2225

AN:

56340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1953

3905

5858

7810

9763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1016

2032

3048

4064

5080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0636

AC:

9687

AN:

152284

Hom.:

596

Cov.:

AF XY:

0.0646

AC XY:

4811

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.152

AC:

6295

AN:

41516

American (AMR)

AF:

0.0553

AC:

846

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3472

East Asian (EAS)

AF:

0.0345

AC:

179

AN:

5190

South Asian (SAS)

AF:

0.0982

AC:

474

AN:

4828

European-Finnish (FIN)

AF:

0.0174

AC:

185

AN:

10622

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0217

AC:

1479

AN:

68032

Other (OTH)

AF:

0.0667

AC:

141

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

444

887

1331

1774

2218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0412

Hom.:

Bravo

AF:

0.0682

Asia WGS

AF:

0.120

AC:

415

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

(source)

DANN

Benign

0.49

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over