chr14-94233756-A-T

Variant names:

• chr14-94233756-A-T
• NM_058237.2:c.620A>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.620A>T​(p.His207Leu) 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. 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: 2.50
• 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=0.18390277).

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.620A>T	p.His207Leu	missense	Exon 6 of 25	NP_478144.1	Q6NUP7-1
	PPP4R4	NM_001348142.2		c.377A>T	p.His126Leu	missense	Exon 6 of 25	NP_001335071.1
	PPP4R4	NM_001348143.2		c.299A>T	p.His100Leu	missense	Exon 8 of 27	NP_001335072.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R4	ENST00000304338.8	TSL:1 MANE Select	c.620A>T	p.His207Leu	missense	Exon 6 of 25	ENSP00000305924.3	Q6NUP7-1
	PPP4R4	ENST00000903467.1		c.620A>T	p.His207Leu	missense	Exon 6 of 25	ENSP00000573526.1
	PPP4R4	ENST00000941299.1		c.620A>T	p.His207Leu	missense	Exon 6 of 24	ENSP00000611358.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

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	0.073
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.33
Sift	Benign	0.42	T
Sift4G	Benign	0.31	T
Polyphen		0.028	B
Vest4		0.29
MutPred		0.48		Gain of catalytic residue at A206 (P = 0.0265)
MVP		0.55
MPC		0.35
ClinPred		0.38	T
GERP RS		1.6
Varity_R		0.14
gMVP		0.22
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr14-94700093;