Genetic Variant NM_001135629.3:c.-121_-119delGGC (chr2-48440812-CGCG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001135629.3(PPP1R21):c.-121_-119delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 606,200 control chromosomes in the GnomAD database, including 2,467 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.093 ( 727 hom., cov: 24)

Exomes 𝑓: 0.091 ( 1740 hom. )

Consequence

PPP1R21
NM_001135629.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

Publications

4 publications found

Variant links:

Genes affected

PPP1R21 (HGNC:30595): (protein phosphatase 1 regulatory subunit 21) Located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

PPP1R21 links:

PPP1R21-DT (HGNC:55206): (PPP1R21 divergent transcript)

PPP1R21-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 2-48440812-CGCG-C is Benign according to our data. Variant chr2-48440812-CGCG-C is described in ClinVar as [Benign]. Clinvar id is 3910185.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3 link	c.-121_-119delGGC		5_prime_UTR_variant	Exon 1 of 22	ENST00000294952.13	NP_001129101.1	Q6ZMI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R21	ENST00000294952.13 link	c.-121_-119delGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8		Q6ZMI0-1

Frequencies

GnomAD3 genomes

AF:

0.0929

AC:

14074

AN:

151438

Hom.:

726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.0387

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0909

GnomAD4 exome

AF:

0.0909

AC:

41305

AN:

454644

Hom.:

1740

AF XY:

0.0861

AC XY:

21050

AN XY:

244556

show subpopulations

African (AFR)

AF:

0.0766

AC:

730

AN:

9524

American (AMR)

AF:

0.0438

AC:

774

AN:

17676

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

661

AN:

14196

East Asian (EAS)

AF:

0.00248

AC:

AN:

24572

South Asian (SAS)

AF:

0.0243

AC:

1145

AN:

47136

European-Finnish (FIN)

AF:

0.136

AC:

5594

AN:

41186

Middle Eastern (MID)

AF:

0.0250

AC:

AN:

1958

European-Non Finnish (NFE)

AF:

0.110

AC:

30066

AN:

273092

Other (OTH)

AF:

0.0879

AC:

2225

AN:

25304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1585

3169

4754

6338

7923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0929

AC:

14086

AN:

151556

Hom.:

727

Cov.:

AF XY:

0.0909

AC XY:

6731

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.0835

AC:

3462

AN:

41438

American (AMR)

AF:

0.0623

AC:

950

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.0387

AC:

134

AN:

3460

East Asian (EAS)

AF:

0.000591

AC:

AN:

5076

South Asian (SAS)

AF:

0.0143

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.134

AC:

1405

AN:

10476

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.114

AC:

7754

AN:

67726

Other (OTH)

AF:

0.0895

AC:

189

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

620

1240

1860

2480

3100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0481

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=299/1

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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NM_001135629.3:c.-121_-119delGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over