NM_001300783.2:c.667C>G

Variant names:

• chr5-120686461-C-G
• rs959340844
• NM_001300783.2:c.667C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300783.2(PRR16):​c.667C>G​(p.Arg223Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R223Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRR16 NM_001300783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• Publications: 0 publications found

Genes affected

PRR16 (HGNC:29654): (proline rich 16) Involved in positive regulation of cell size and positive regulation of translation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3091271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300783.2. 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
	PRR16	NM_001300783.2	MANE Select	c.667C>G	p.Arg223Gly	missense	Exon 2 of 2	NP_001287712.1	Q569H4-1
	PRR16	NM_016644.3		c.598C>G	p.Arg200Gly	missense	Exon 3 of 3	NP_057728.1	Q569H4-3
	PRR16	NM_001308087.2		c.457C>G	p.Arg153Gly	missense	Exon 2 of 2	NP_001295016.1	Q569H4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR16	ENST00000407149.7	TSL:1 MANE Select	c.667C>G	p.Arg223Gly	missense	Exon 2 of 2	ENSP00000385118.2	Q569H4-1
	PRR16	ENST00000379551.2	TSL:1	c.598C>G	p.Arg200Gly	missense	Exon 3 of 3	ENSP00000368869.2	Q569H4-3
	PRR16	ENST00000446965.2	TSL:1	c.508C>G	p.Arg170Gly	missense	Exon 3 of 3	ENSP00000405491.2	A0A0A0MSW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.86	T
PhyloP100		4.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.13
Sift	Uncertain	0.020	D
Sift4G	Benign	0.11	T
Polyphen		0.95	P
Vest4		0.42
MutPred		0.28		Gain of loop (P = 0.0502)
MVP		0.13
MPC		0.28
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.18
gMVP		0.20
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs959340844; hg19: chr5-120022156;