22-31713654-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_173566.3(PRR14L):c.4185G>C(p.Leu1395Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,551,944 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0010 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (25 hom.)
• Consequence: PRR14L NM_173566.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

Genes affected

PRR14L (HGNC:28738): (proline rich 14 like)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004124522).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00101 (153/152220) while in subpopulation EAS AF= 0.0256 (133/5186). AF 95% confidence interval is 0.0221. There are 3 homozygotes in gnomad4. There are 86 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR14L	NM_173566.3	c.4185G>C	p.Leu1395Phe	missense_variant	4/9	ENST00000327423.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR14L	ENST00000327423.11	c.4185G>C	p.Leu1395Phe	missense_variant	4/9	5	NM_173566.3	P1
PRR14L	ENST00000431684.1	c.192G>C	p.Leu64Phe	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 152 AN: 152102 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00152 AC: 239 AN: 157744 Hom.: 1 AF XY: 0.00157 AC XY: 131 AN XY: 83312

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00176

Gnomad EAS exome AF: 0.0176

Gnomad SAS exome AF: 0.000571

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.00202

GnomAD4 exome AF: 0.00100 AC: 1405 AN: 1399724 Hom.: 25 Cov.: 34 AF XY: 0.00104 AC XY: 718 AN XY: 690346

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000840

Gnomad4 ASJ exome AF: 0.00159

Gnomad4 EAS exome AF: 0.0322

Gnomad4 SAS exome AF: 0.000883

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000853

Gnomad4 OTH exome AF: 0.000792

GnomAD4 genome AF: 0.00101 AC: 153 AN: 152220 Hom.: 3 Cov.: 32 AF XY: 0.00116 AC XY: 86 AN XY: 74418

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0256

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.00104

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000629 AC: 2

ExAC AF: 0.00106 AC: 27

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	11
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.038
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.022	D
Polyphen		0.082	B
Vest4		0.046
MutPred		0.073		Loss of disorder (P = 0.1357);
MVP		0.068
MPC		0.073
ClinPred		0.013	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.073
gMVP		0.042

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

Publications

LitVar

Other links and lift over

dbSNP: rs3804090; hg19: chr22-32109640; COSMIC: COSV57883406; COSMIC: COSV57883406;