chr7-29566478-C-T

Variant names:

• chr7-29566478-C-T
• rs757043478
• NM_175887.3:c.149C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_175887.3(PRR15):​c.149C>T​(p.Pro50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,599,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: PRR15 NM_175887.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.824
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03545791).

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.149C>T	p.Pro50Leu	missense	Exon 2 of 2	NP_787083.1	Q8IV56
	PRR15	NM_001329996.2		c.149C>T	p.Pro50Leu	missense	Exon 2 of 2	NP_001316925.1	Q8IV56
	PRR15	NM_001329997.1		c.149C>T	p.Pro50Leu	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.149C>T	p.Pro50Leu	missense	Exon 2 of 2	ENSP00000317836.2	Q8IV56
	PRR15	ENST00000878802.1		c.149C>T	p.Pro50Leu	missense	Exon 2 of 2	ENSP00000548861.1
	PRR15	ENST00000878803.1		c.149C>T	p.Pro50Leu	missense	Exon 2 of 2	ENSP00000548862.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000234 AC: 5 AN: 213322 AF XY: 0.0000426

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: 0.000103

Gnomad NFE exome AF: 0.0000329

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000304 AC: 44 AN: 1446940 Hom.: 0 Cov.: 66 AF XY: 0.0000320 AC XY: 23 AN XY: 718536

African (AFR) AF: 0.00 AC: 0 AN: 32970

American (AMR) AF: 0.00 AC: 0 AN: 43060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.00 AC: 0 AN: 38860

South Asian (SAS) AF: 0.00 AC: 0 AN: 84672

European-Finnish (FIN) AF: 0.0000393 AC: 2 AN: 50866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000362 AC: 40 AN: 1105136

Other (OTH) AF: 0.0000335 AC: 2 AN: 59788

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74366

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000334 AC: 4

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	Benign	0.091
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.82
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.047
Sift	Benign	0.23	T
Sift4G	Benign	0.40	T
Polyphen		0.015	B
Vest4		0.069
MutPred		0.19		Gain of catalytic residue at P50 (P = 0.0104)
MVP		0.030
MPC		0.40
ClinPred		0.085	T
GERP RS		1.1
Varity_R		0.054
gMVP		0.22
Mutation Taster		=95/5	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: rs757043478; hg19: chr7-29606094;