chr14-94174485-C-T

Variant names:

• chr14-94174485-C-T
• NM_058237.2:c.20C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058237.2(PPP4R4):​c.20C>T​(p.Ala7Val) 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: 33)
• Consequence: PPP4R4 NM_058237.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.100
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105520815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058237.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R4	NM_058237.2	MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 25	NP_478144.1	Q6NUP7-1
	PPP4R4	NM_001348145.2		c.20C>T	p.Ala7Val	missense	Exon 1 of 5	NP_001335074.1
	PPP4R4	NM_020958.3		c.20C>T	p.Ala7Val	missense	Exon 1 of 5	NP_066009.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R4	ENST00000304338.8	TSL:1 MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 25	ENSP00000305924.3	Q6NUP7-1
	PPP4R4	ENST00000328839.3	TSL:1	c.20C>T	p.Ala7Val	missense	Exon 1 of 5	ENSP00000330831.3	Q6NUP7-2
	PPP4R4	ENST00000903467.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 25	ENSP00000573526.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.10
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.0070
Sift	Benign	0.18	T
Sift4G	Benign	0.35	T
Polyphen		0.048	B
Vest4		0.12
MutPred		0.30		Gain of catalytic residue at P3 (P = 0)
MVP		0.030
MPC		0.28
ClinPred		0.10	T
GERP RS		1.9
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.021
gMVP		0.29
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr14-94640822;