chr7-29566615-C-T

Variant names:

• chr7-29566615-C-T
• rs1465072080
• NM_175887.3:c.286C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_175887.3(PRR15):​c.286C>T​(p.Arg96Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,954 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR15 NM_175887.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

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.286C>T	p.Arg96Cys	missense	Exon 2 of 2	NP_787083.1	Q8IV56
	PRR15	NM_001329996.2		c.286C>T	p.Arg96Cys	missense	Exon 2 of 2	NP_001316925.1	Q8IV56
	PRR15	NM_001329997.1		c.286C>T	p.Arg96Cys	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.286C>T	p.Arg96Cys	missense	Exon 2 of 2	ENSP00000317836.2	Q8IV56
	PRR15	ENST00000878802.1		c.286C>T	p.Arg96Cys	missense	Exon 2 of 2	ENSP00000548861.1
	PRR15	ENST00000878803.1		c.286C>T	p.Arg96Cys	missense	Exon 2 of 2	ENSP00000548862.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000449 AC: 1 AN: 222810 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450954 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 720840

African (AFR) AF: 0.00 AC: 0 AN: 33138

American (AMR) AF: 0.00 AC: 0 AN: 43786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39108

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107268

Other (OTH) AF: 0.00 AC: 0 AN: 59916

GnomAD4 genome Cov.: 33

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	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Benign	2.0	M
PhyloP100		2.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.34		Loss of methylation at R96 (P = 0.0428)
MVP		0.58
MPC		1.4
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.84
gMVP		0.35
Mutation Taster		=66/34	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: rs1465072080; hg19: chr7-29606231;