rs759341558

Variant names:

• chr5-120686024-C-A
• rs759341558
• NM_001300783.2:c.230C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-120686024-C-A
• chr5-120686024-C-T

Variant summary

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

The NM_001300783.2(PRR16):​c.230C>A​(p.Thr77Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T77M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR16 NM_001300783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 4 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.230C>A	p.Thr77Lys	missense	Exon 2 of 2	NP_001287712.1	Q569H4-1
	PRR16	NM_016644.3		c.161C>A	p.Thr54Lys	missense	Exon 3 of 3	NP_057728.1	Q569H4-3
	PRR16	NM_001308087.2		c.20C>A	p.Thr7Lys	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.230C>A	p.Thr77Lys	missense	Exon 2 of 2	ENSP00000385118.2	Q569H4-1
	PRR16	ENST00000379551.2	TSL:1	c.161C>A	p.Thr54Lys	missense	Exon 3 of 3	ENSP00000368869.2	Q569H4-3
	PRR16	ENST00000446965.2	TSL:1	c.71C>A	p.Thr24Lys	missense	Exon 3 of 3	ENSP00000405491.2	A0A0A0MSW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251352 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.59	T
PhyloP100		7.5
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.14		Gain of ubiquitination at T77 (P = 0.0031)
MVP		0.32
MPC		0.29
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.50
Mutation Taster		=27/73	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: rs759341558; hg19: chr5-120021719;