5-120686030-C-G

Variant names:

• chr5-120686030-C-G
• rs201082218
• NM_001300783.2:c.236C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001300783.2(PRR16):​c.236C>G​(p.Thr79Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T79M) 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: 7.54
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.236C>G	p.Thr79Arg	missense	Exon 2 of 2	NP_001287712.1	Q569H4-1
	PRR16	NM_016644.3		c.167C>G	p.Thr56Arg	missense	Exon 3 of 3	NP_057728.1	Q569H4-3
	PRR16	NM_001308087.2		c.26C>G	p.Thr9Arg	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.236C>G	p.Thr79Arg	missense	Exon 2 of 2	ENSP00000385118.2	Q569H4-1
	PRR16	ENST00000379551.2	TSL:1	c.167C>G	p.Thr56Arg	missense	Exon 3 of 3	ENSP00000368869.2	Q569H4-3
	PRR16	ENST00000446965.2	TSL:1	c.77C>G	p.Thr26Arg	missense	Exon 3 of 3	ENSP00000405491.2	A0A0A0MSW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.45	T
PhyloP100		7.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.18		Loss of phosphorylation at T79 (P = 0.0156)
MVP		0.41
MPC		0.29
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.81
gMVP		0.58
Mutation Taster		=34/66	disease causing

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: rs201082218; hg19: chr5-120021725;