5-120686049-T-A

Variant names:

• chr5-120686049-T-A
• NM_001300783.2:c.255T>A

Variant summary

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

The NM_001300783.2(PRR16):​c.255T>A​(p.Ser85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRR16 NM_001300783.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.38
• 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=0.34555927).

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.255T>A	p.Ser85Arg	missense	Exon 2 of 2	NP_001287712.1	Q569H4-1
	PRR16	NM_016644.3		c.186T>A	p.Ser62Arg	missense	Exon 3 of 3	NP_057728.1	Q569H4-3
	PRR16	NM_001308087.2		c.45T>A	p.Ser15Arg	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.255T>A	p.Ser85Arg	missense	Exon 2 of 2	ENSP00000385118.2	Q569H4-1
	PRR16	ENST00000379551.2	TSL:1	c.186T>A	p.Ser62Arg	missense	Exon 3 of 3	ENSP00000368869.2	Q569H4-3
	PRR16	ENST00000446965.2	TSL:1	c.96T>A	p.Ser32Arg	missense	Exon 3 of 3	ENSP00000405491.2	A0A0A0MSW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461860 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727230

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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: 0.00000180 AC: 2 AN: 1111994

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	5.5
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.53	T
PhyloP100		-1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.76
MutPred		0.26		Loss of glycosylation at S85 (P = 0.0049)
MVP		0.38
MPC		0.28
ClinPred		0.97	D
GERP RS		-4.3
Varity_R		0.77
gMVP		0.58
Mutation Taster		=21/79	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

hg19: chr5-120021744;