Genetic Variant PRR33:p.Ala5Ala (chr11-1890570-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001395380.1(PRR33):c.15T>C(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 708,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

PRR33
NM_001395380.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.25

Publications

0 publications found

Variant links:

Genes affected

PRR33 (HGNC:35118): (proline rich 33) Predicted to act upstream of or within response to wounding. [provided by Alliance of Genome Resources, Apr 2022]

PRR33 links:

LSP1 (HGNC:6707): (lymphocyte specific protein 1) This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

LSP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 11-1890570-A-G is Benign according to our data. Variant chr11-1890570-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641352.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.25 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395380.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRR33	NM_001395380.1	MANE Select	c.15T>C	p.Ala5Ala	synonymous	Exon 1 of 1	NP_001382309.1	A0A1W2PPC1
LSP1	NM_002339.3	MANE Select	c.*14-1203A>G		intron	N/A	NP_002330.1	P33241-1
LSP1	NM_001242932.2		c.*14-1203A>G		intron	N/A	NP_001229861.1	P33241-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRR33	ENST00000640310.2	TSL:6 MANE Select	c.15T>C	p.Ala5Ala	synonymous	Exon 1 of 1	ENSP00000491327.1	A0A1W2PPC1
LSP1	ENST00000311604.8	TSL:1 MANE Select	c.*14-1203A>G		intron	N/A	ENSP00000308383.4	P33241-1
LSP1	ENST00000381775.5	TSL:2	c.*14-1203A>G		intron	N/A	ENSP00000371194.1	P33241-3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000105

AC:

AN:

142324

AF XY:

0.0000907

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000862

AC:

AN:

556862

Hom.:

Cov.:

AF XY:

0.0000764

AC XY:

AN XY:

301176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15796

American (AMR)

AF:

0.000115

AC:

AN:

34706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20006

East Asian (EAS)

AF:

0.00

AC:

AN:

32102

South Asian (SAS)

AF:

0.0000159

AC:

AN:

62744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3702

European-Non Finnish (NFE)

AF:

0.000129

AC:

AN:

316936

Other (OTH)

AF:

0.0000654

AC:

AN:

30602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000797

Hom.:

Bravo

AF:

0.0000831

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.67

(source)

DANN

Benign

0.22

PhyloP100

-2.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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