22-31712593-A-G

Position:

• chr22-31712593-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173566.3(PRR14L):​c.5246T>C​(p.Leu1749Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR14L NM_173566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1968858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR14L	NM_173566.3	c.5246T>C	p.Leu1749Ser	missense_variant	4/9	ENST00000327423.11	NP_775837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR14L	ENST00000327423.11	c.5246T>C	p.Leu1749Ser	missense_variant	4/9	5	NM_173566.3	ENSP00000331845	P1
PRR14L	ENST00000330495.8	c.155T>C	p.Leu52Ser	missense_variant	1/6	1		ENSP00000332169
PRR14L	ENST00000431684.1	c.1253T>C	p.Leu418Ser	missense_variant, NMD_transcript_variant	1/5	2		ENSP00000389527

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399396 Hom.: 0 Cov.: 34 AF XY: 0.00000290 AC XY: 2 AN XY: 690196

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: 0.00000185

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

Jan 31, 2023

The c.5246T>C (p.L1749S) alteration is located in exon 4 (coding exon 3) of the PRR14L gene. This alteration results from a T to C substitution at nucleotide position 5246, causing the leucine (L) at amino acid position 1749 to be replaced by a serine (S). 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	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.83	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.064
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.32
MutPred		0.42		Gain of loop (P = 0.0013);
MVP		0.043
MPC		0.41
ClinPred		0.94	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-32108579;