NM_001160167.2:c.776C>T

Variant names:

• chr11-36462405-C-T
• rs557394432
• NM_001160167.2:c.776C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001160167.2(PRR5L):​c.776C>T​(p.Ala259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000485 in 1,568,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000052 (1 hom.)
• Consequence: PRR5L NM_001160167.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457
• Publications: 0 publications found

Genes affected

PRR5L (HGNC:25878): (proline rich 5 like) Enables ubiquitin protein ligase binding activity. Involved in several processes, including TORC2 signaling; positive regulation of mRNA catabolic process; and regulation of fibroblast migration. Part of TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023208678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160167.2. 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
	PRR5L	NM_001160167.2	MANE Select	c.776C>T	p.Ala259Val	missense	Exon 9 of 9	NP_001153639.1	Q6MZQ0-1
	PRR5L	NM_024841.5		c.776C>T	p.Ala259Val	missense	Exon 10 of 10	NP_079117.3
	PRR5L	NM_001160168.2		c.392C>T	p.Ala131Val	missense	Exon 6 of 6	NP_001153640.1	Q6MZQ0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR5L	ENST00000530639.6	TSL:2 MANE Select	c.776C>T	p.Ala259Val	missense	Exon 9 of 9	ENSP00000435050.1	Q6MZQ0-1
	PRR5L	ENST00000378867.7	TSL:1	c.776C>T	p.Ala259Val	missense	Exon 10 of 10	ENSP00000368144.3	Q6MZQ0-1
	PRR5L	ENST00000530627.1	TSL:1	n.222C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000786 AC: 17 AN: 216156 AF XY: 0.0000954

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: 0.0000514

Gnomad OTH exome AF: 0.000191

GnomAD4 exome AF: 0.0000516 AC: 73 AN: 1415994 Hom.: 1 Cov.: 30 AF XY: 0.0000701 AC XY: 49 AN XY: 698560

African (AFR) AF: 0.00 AC: 0 AN: 32602

American (AMR) AF: 0.00 AC: 0 AN: 40662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39140

South Asian (SAS) AF: 0.000506 AC: 40 AN: 79004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51002

Middle Eastern (MID) AF: 0.00145 AC: 8 AN: 5526

European-Non Finnish (NFE) AF: 0.0000221 AC: 24 AN: 1086664

Other (OTH) AF: 0.0000171 AC: 1 AN: 58408

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000907 AC: 11

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.075
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.46
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.070
Sift	Benign	0.37	T
Sift4G	Benign	0.52	T
Polyphen		0.013	B
Vest4		0.051
MutPred		0.32		Gain of loop (P = 0.0166)
MVP		0.20
MPC		0.27
ClinPred		0.034	T
GERP RS		4.3
Varity_R		0.066
gMVP		0.22
Mutation Taster		=89/11	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: rs557394432; hg19: chr11-36483955;