22-31701677-A-G

Position:

• chr22-31701677-A-G

Variant summary

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

The NM_173566.3(PRR14L):​c.6086T>C​(p.Met2029Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.93

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	Protein	UniProt
PRR14L	NM_173566.3	c.6086T>C	p.Met2029Thr	missense_variant	7/9	ENST00000327423.11	NP_775837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR14L	ENST00000327423.11	c.6086T>C	p.Met2029Thr	missense_variant	7/9	5	NM_173566.3	ENSP00000331845	P1
PRR14L	ENST00000330495.8	c.995T>C	p.Met332Thr	missense_variant	4/6	1		ENSP00000332169
PRR14L	ENST00000432485.1	c.257T>C	p.Met86Thr	missense_variant, NMD_transcript_variant	2/5	2		ENSP00000399381
PRR14L	ENST00000431684.1	c.2007+1873T>C		intron_variant, NMD_transcript_variant		2		ENSP00000389527

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 08, 2024

The c.6086T>C (p.M2029T) alteration is located in exon 7 (coding exon 6) of the PRR14L gene. This alteration results from a T to C substitution at nucleotide position 6086, causing the methionine (M) at amino acid position 2029 to be replaced by a threonine (T). 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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.25		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.22
MPC		2.0
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.82
gMVP		0.91

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: chr22-32097663;