17-59185196-A-T

Variant names:

• chr17-59185196-A-T
• rs145164508
• NM_018304.4:c.271A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018304.4(PRR11):​c.271A>T​(p.Ile91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. I91V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRR11 NM_018304.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 3 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: 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=0.06539908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR11	NM_018304.4	c.271A>T	p.Ile91Leu	missense_variant	Exon 3 of 10	ENST00000262293.9	NP_060774.2
PRR11	XM_024450828.2	c.271A>T	p.Ile91Leu	missense_variant	Exon 4 of 11		XP_024306596.1
PRR11	XM_047436387.1	c.271A>T	p.Ile91Leu	missense_variant	Exon 4 of 11		XP_047292343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR11	ENST00000262293.9	c.271A>T	p.Ile91Leu	missense_variant	Exon 3 of 10	1	NM_018304.4	ENSP00000262293.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251002 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000615

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461686 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.015	T;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.62	.;T;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.065	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.;L
PhyloP100		0.56
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.73	N;.;.;.
REVEL	Benign	0.071
Sift	Benign	0.25	T;.;.;.
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.021	B;.;.;B
Vest4		0.25
MutPred		0.25		Gain of catalytic residue at I91 (P = 0.0213);Gain of catalytic residue at I91 (P = 0.0213);.;Gain of catalytic residue at I91 (P = 0.0213);
MVP		0.15
MPC		0.15
ClinPred		0.029	T
GERP RS		-5.7
Varity_R		0.051
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs145164508; hg19: chr17-57262557;