Genetic Variant NM_178553.4:c.-25C>T (chr2-27138354-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178553.4(PRR30):c.-25C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,569,448 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0043 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 192 hom. )

Consequence

PRR30
NM_178553.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.141

Publications

2 publications found

Variant links:

Genes affected

PRR30 (HGNC:28677): (proline rich 30)

PRR30 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR30	NM_178553.4 link	c.-25C>T		5_prime_UTR_variant	Exon 3 of 3	ENST00000335524.7	NP_848648.2	Q53SZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR30	ENST00000335524.7 link	c.-25C>T		5_prime_UTR_variant	Exon 3 of 3	1	NM_178553.4	ENSP00000335017.3		Q53SZ7
PRR30	ENST00000432962.2 link	c.-25C>T		5_prime_UTR_variant	Exon 3 of 4	3		ENSP00000393468.2		C9JVA3

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

653

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0727

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00863

AC:

1846

AN:

213908

AF XY:

0.00753

show subpopulations

Gnomad AFR exome

AF:

0.000699

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.000165

Gnomad EAS exome

AF:

0.0739

Gnomad FIN exome

AF:

0.00387

Gnomad NFE exome

AF:

0.000303

Gnomad OTH exome

AF:

0.00476

GnomAD4 exome

AF:

0.00348

AC:

4937

AN:

1417148

Hom.:

192

Cov.:

AF XY:

0.00336

AC XY:

2356

AN XY:

700662

show subpopulations

African (AFR)

AF:

0.000439

AC:

AN:

31912

American (AMR)

AF:

0.0118

AC:

461

AN:

39068

Ashkenazi Jewish (ASJ)

AF:

0.000524

AC:

AN:

22880

East Asian (EAS)

AF:

0.0927

AC:

3643

AN:

39316

South Asian (SAS)

AF:

0.00144

AC:

115

AN:

79770

European-Finnish (FIN)

AF:

0.00313

AC:

162

AN:

51702

Middle Eastern (MID)

AF:

0.000511

AC:

AN:

3914

European-Non Finnish (NFE)

AF:

0.000220

AC:

240

AN:

1090376

Other (OTH)

AF:

0.00495

AC:

288

AN:

58210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

287

574

862

1149

1436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.00427

AC:

650

AN:

152300

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

360

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41564

American (AMR)

AF:

0.00994

AC:

152

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0727

AC:

376

AN:

5172

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68028

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00159

Hom.:

Bravo

AF:

0.00506

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.7

(source)

DANN

Benign

0.71

PhyloP100

-0.14

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over