22-31703612-C-T

Variant summary

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

The NM_173566.3(PRR14L):c.5938G>A(p.Glu1980Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 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: 6.8e-7 (0 hom.)
• Consequence: PRR14L NM_173566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

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.5938G>A	p.Glu1980Lys	missense_variant	6/9	ENST00000327423.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR14L	ENST00000327423.11	c.5938G>A	p.Glu1980Lys	missense_variant	6/9	5	NM_173566.3	P1
PRR14L	ENST00000330495.8	c.847G>A	p.Glu283Lys	missense_variant	3/6	1
PRR14L	ENST00000431684.1	c.1945G>A	p.Glu649Lys	missense_variant, NMD_transcript_variant	3/5	2
PRR14L	ENST00000432485.1	c.109G>A	p.Glu37Lys	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jun 21, 2022

The c.5938G>A (p.E1980K) alteration is located in exon 6 (coding exon 5) of the PRR14L gene. This alteration results from a G to A substitution at nucleotide position 5938, causing the glutamic acid (E) at amino acid position 1980 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	0.84	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.21		Gain of ubiquitination at E1980 (P = 0.0085);
MVP		0.17
MPC		0.42
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.25
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr22-32099598; COSMIC: COSV105218814; COSMIC: COSV105218814;