NM_175887.3:c.128C>T

Variant names:

• chr7-29566457-C-T
• rs1283362926
• NM_175887.3:c.128C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175887.3(PRR15):​c.128C>T​(p.Thr43Met) 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 1,447,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. T43K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR15 NM_175887.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080854416).

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.128C>T	p.Thr43Met	missense	Exon 2 of 2	NP_787083.1	Q8IV56
	PRR15	NM_001329996.2		c.128C>T	p.Thr43Met	missense	Exon 2 of 2	NP_001316925.1	Q8IV56
	PRR15	NM_001329997.1		c.128C>T	p.Thr43Met	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.128C>T	p.Thr43Met	missense	Exon 2 of 2	ENSP00000317836.2	Q8IV56
	PRR15	ENST00000878802.1		c.128C>T	p.Thr43Met	missense	Exon 2 of 2	ENSP00000548861.1
	PRR15	ENST00000878803.1		c.128C>T	p.Thr43Met	missense	Exon 2 of 2	ENSP00000548862.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447640 Hom.: 0 Cov.: 65 AF XY: 0.00000278 AC XY: 2 AN XY: 719142

African (AFR) AF: 0.00 AC: 0 AN: 33046

American (AMR) AF: 0.00 AC: 0 AN: 43170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.00 AC: 0 AN: 38954

South Asian (SAS) AF: 0.00 AC: 0 AN: 84908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105454

Other (OTH) AF: 0.00 AC: 0 AN: 59778

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.9
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.95
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.072
Sift	Benign	0.13	T
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.17
MutPred		0.20		Loss of phosphorylation at T43 (P = 0.0015)
MVP		0.048
MPC		0.48
ClinPred		0.24	T
GERP RS		-0.28
Varity_R		0.019
gMVP		0.20
Mutation Taster		=98/2	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: rs1283362926; hg19: chr7-29606073;