chr22-31703600-C-T

Position:

• chr22-31703600-C-T

Variant summary

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

The NM_173566.3(PRR14L):​c.5950G>A​(p.Val1984Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR14L NM_173566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00

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=0.15509066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR14L	NM_173566.3	c.5950G>A	p.Val1984Met	missense_variant	6/9	ENST00000327423.11	NP_775837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR14L	ENST00000327423.11	c.5950G>A	p.Val1984Met	missense_variant	6/9	5	NM_173566.3	ENSP00000331845.6
PRR14L	ENST00000330495.8	c.856G>A	p.Val286Met	missense_variant	3/6	1		ENSP00000332169.4
PRR14L	ENST00000431684.1	n.1957G>A		non_coding_transcript_exon_variant	3/5	2		ENSP00000389527.1
PRR14L	ENST00000432485.1	n.118G>A		non_coding_transcript_exon_variant	1/5	2		ENSP00000399381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 06, 2023

The c.5950G>A (p.V1984M) 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 5950, causing the valine (V) at amino acid position 1984 to be replaced by a methionine (M). 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	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.027	D
Polyphen		0.98	D
Vest4		0.29
MutPred		0.11		Gain of helix (P = 0.062);
MVP		0.068
MPC		1.8
ClinPred		0.62	D
GERP RS		2.2
Varity_R		0.074
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr22-32099586;