rs1892408330

Variant names:

• chr14-94237579-A-C
• NM_058237.2:c.746A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-94237579-A-C
• chr14-94237579-A-G

Variant summary

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

The NM_058237.2(PPP4R4):​c.746A>C​(p.Lys249Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K249R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP4R4 NM_058237.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18

Genes affected

PPP4R4 (HGNC:23788): (protein phosphatase 4 regulatory subunit 4) The protein encoded by this gene is a HEAT-like repeat-containing protein. The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins. Arrays of HEAT repeats form a rod-like helical structure and appear to function as protein-protein interaction surfaces. The repeat-containing region of this protein has some similarity to the constant regulatory domain of the protein phosphatase 2A PR65/A subunit. The encoded protein binds protein serine/threonine phosphatase 4c in the cytoplasm. [provided by RefSeq, Jan 2017]

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 rank	MANE	Protein	UniProt
PPP4R4	NM_058237.2	c.746A>C	p.Lys249Thr	missense_variant	Exon 8 of 25	ENST00000304338.8	NP_478144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP4R4	ENST00000304338.8	c.746A>C	p.Lys249Thr	missense_variant	Exon 8 of 25	1	NM_058237.2	ENSP00000305924.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.39	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.47
MutPred		0.48		Gain of catalytic residue at T248 (P = 0);
MVP		0.64
MPC		1.0
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.43
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr14-94703916;