7-29566652-T-G

Variant names:

• chr7-29566652-T-G
• rs1171255319
• NM_175887.3:c.323T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_175887.3(PRR15):​c.323T>G​(p.Leu108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,584,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PRR15 NM_175887.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

Genes affected

PRR15 (HGNC:22310): (proline rich 15)

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175887.3. 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
	PRR15	NM_175887.3	MANE Select	c.323T>G	p.Leu108Arg	missense	Exon 2 of 2	NP_787083.1	Q8IV56
	PRR15	NM_001329996.2		c.323T>G	p.Leu108Arg	missense	Exon 2 of 2	NP_001316925.1	Q8IV56
	PRR15	NM_001329997.1		c.323T>G	p.Leu108Arg	missense	Exon 2 of 2	NP_001316926.1	A4D1A1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR15	ENST00000319694.3	TSL:1 MANE Select	c.323T>G	p.Leu108Arg	missense	Exon 2 of 2	ENSP00000317836.2	Q8IV56
	PRR15	ENST00000878802.1		c.323T>G	p.Leu108Arg	missense	Exon 2 of 2	ENSP00000548861.1
	PRR15	ENST00000878803.1		c.323T>G	p.Leu108Arg	missense	Exon 2 of 2	ENSP00000548862.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432042 Hom.: 0 Cov.: 66 AF XY: 0.00000141 AC XY: 1 AN XY: 709676

African (AFR) AF: 0.0000307 AC: 1 AN: 32576

American (AMR) AF: 0.00 AC: 0 AN: 41232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00 AC: 0 AN: 37678

South Asian (SAS) AF: 0.00 AC: 0 AN: 82182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097718

Other (OTH) AF: 0.00 AC: 0 AN: 59146

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

African (AFR) AF: 0.0000724 AC: 3 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000340

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	0.60
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.17		Gain of methylation at L108 (P = 0.0134)
MVP		0.42
MPC		1.5
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.74
gMVP		0.17
Mutation Taster		=59/41	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: rs1171255319; hg19: chr7-29606268;