Genetic Variant PRR11:p.Ala216Ser (chr17-59194757-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018304.4(PRR11):c.646G>T(p.Ala216Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A216P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRR11
NM_018304.4 missense, splice_region

Scores

Splicing: ADA: 0.07065

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Publications

0 publications found

Variant links:

Genes affected

PRR11 (HGNC:25619): (proline rich 11) Involved in regulation of cell cycle. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRR11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025025874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018304.4. 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
	PRR11	NM_018304.4	MANE Select	c.646G>T	p.Ala216Ser	missense splice_region	Exon 6 of 10	NP_060774.2	D2SNZ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRR11	ENST00000262293.9	TSL:1 MANE Select	c.646G>T	p.Ala216Ser	missense splice_region	Exon 6 of 10	ENSP00000262293.5	Q96HE9
PRR11	ENST00000614081.1	TSL:1	c.646G>T	p.Ala216Ser	missense splice_region	Exon 6 of 11	ENSP00000481852.1	Q96HE9
PRR11	ENST00000580177.5	TSL:1	n.646G>T		splice_region non_coding_transcript_exon	Exon 6 of 11	ENSP00000463733.1	Q96HE9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249452

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33300

American (AMR)

AF:

0.0000226

AC:

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

85770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109470

Other (OTH)

AF:

0.00

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.6

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

M_CAP

Benign

0.0014

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.077

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.36

REVEL

Benign

0.016

Sift

Benign

0.36

Sift4G

Benign

0.44

Polyphen

0.0090

Vest4

0.037

MutPred

0.12

Gain of glycosylation at A216 (P = 0.0093)

MVP

0.32

MPC

0.16

ClinPred

0.018

GERP RS

-1.6

Varity_R

0.027

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.071

dbscSNV1_RF

Benign

0.48

SpliceAI score (max)

0.15

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over