NM_018304.4:c.20G>A

Variant names:

• chr17-59169772-G-A
• rs145780567
• NM_018304.4:c.20G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018304.4(PRR11):​c.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00805 in 1,596,020 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (54 hom.)
• Consequence: PRR11 NM_018304.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.530
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053979754).
• BP6: Variant 17-59169772-G-A is Benign according to our data. Variant chr17-59169772-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2647972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.20G>A	p.Arg7Gln	missense	Exon 2 of 10	NP_060774.2	D2SNZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR11	ENST00000262293.9	TSL:1 MANE Select	c.20G>A	p.Arg7Gln	missense	Exon 2 of 10	ENSP00000262293.5	Q96HE9
	PRR11	ENST00000614081.1	TSL:1	c.20G>A	p.Arg7Gln	missense	Exon 2 of 11	ENSP00000481852.1	Q96HE9
	PRR11	ENST00000580177.5	TSL:1	n.20G>A		non_coding_transcript_exon	Exon 2 of 11	ENSP00000463733.1	Q96HE9

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 952 AN: 151768 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00331

Gnomad AMR AF: 0.00329

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00779

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00609 AC: 1440 AN: 236536 AF XY: 0.00590

Gnomad AFR exome AF: 0.00163

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.00545

Gnomad EAS exome AF: 0.000178

Gnomad FIN exome AF: 0.00902

Gnomad NFE exome AF: 0.00919

Gnomad OTH exome AF: 0.00601

GnomAD4 exome AF: 0.00823 AC: 11892 AN: 1444134 Hom.: 54 Cov.: 30 AF XY: 0.00810 AC XY: 5818 AN XY: 718124

African (AFR) AF: 0.00134 AC: 43 AN: 32094

American (AMR) AF: 0.00299 AC: 119 AN: 39798

Ashkenazi Jewish (ASJ) AF: 0.00555 AC: 141 AN: 25408

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39606

South Asian (SAS) AF: 0.00140 AC: 115 AN: 81940

European-Finnish (FIN) AF: 0.00840 AC: 446 AN: 53088

Middle Eastern (MID) AF: 0.000353 AC: 2 AN: 5658

European-Non Finnish (NFE) AF: 0.00962 AC: 10647 AN: 1107016

Other (OTH) AF: 0.00630 AC: 375 AN: 59526

GnomAD4 genome AF: 0.00626 AC: 951 AN: 151886 Hom.: 6 Cov.: 32 AF XY: 0.00610 AC XY: 453 AN XY: 74232

African (AFR) AF: 0.00167 AC: 69 AN: 41416

American (AMR) AF: 0.00322 AC: 49 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4808

European-Finnish (FIN) AF: 0.00779 AC: 82 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 711 AN: 67954

Other (OTH) AF: 0.00332 AC: 7 AN: 2106

Alfa AF: 0.00768 Hom.: 3

Bravo AF: 0.00573

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00907 AC: 78

ExAC AF: 0.00605 AC: 734

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.53
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.032
Sift	Benign	0.089	T
Sift4G	Benign	0.062	T
Polyphen		0.086	B
Vest4		0.25
MVP		0.52
MPC		0.16
ClinPred		0.0076	T
GERP RS		1.2
Varity_R		0.041
gMVP		0.10
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs145780567; hg19: chr17-57247133; COSMIC: COSV106088298;