22-31712779-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173566.3(PRR14L):c.5060C>A(p.Pro1687His) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,399,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: PRR14L NM_173566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR14L	NM_173566.3	c.5060C>A	p.Pro1687His	missense_variant	4/9	ENST00000327423.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR14L	ENST00000327423.11	c.5060C>A	p.Pro1687His	missense_variant	4/9	5	NM_173566.3	P1
PRR14L	ENST00000431684.1	c.1067C>A	p.Pro356His	missense_variant, NMD_transcript_variant	1/5	2
PRR14L	ENST00000330495.8			upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399622 Hom.: 0 Cov.: 34 AF XY: 0.00000290 AC XY: 2 AN XY: 690296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.0000344

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.5060C>A (p.P1687H) alteration is located in exon 4 (coding exon 3) of the PRR14L gene. This alteration results from a C to A substitution at nucleotide position 5060, causing the proline (P) at amino acid position 1687 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.13
Sift	Benign	0.030	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.36		Gain of helix (P = 0.027);
MVP		0.26
MPC		0.43
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-32108765;