12-19257457-C-T

Variant names:

• chr12-19257457-C-T
• NM_001256470.2:c.457C>T

Variant summary

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

The NM_001256470.2(PLEKHA5):​c.457C>T​(p.His153Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. 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: PLEKHA5 NM_001256470.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38
• Publications: 0 publications found

Genes affected

PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256470.2. 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
	PLEKHA5	NM_001256470.2	MANE Select	c.457C>T	p.His153Tyr	missense	Exon 6 of 32	NP_001243399.1	Q9HAU0-6
	PLEKHA5	NM_001385923.1		c.457C>T	p.His153Tyr	missense	Exon 6 of 31	NP_001372852.1
	PLEKHA5	NM_001385924.1		c.457C>T	p.His153Tyr	missense	Exon 6 of 31	NP_001372853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA5	ENST00000429027.7	TSL:1 MANE Select	c.457C>T	p.His153Tyr	missense	Exon 6 of 32	ENSP00000404296.2	Q9HAU0-6
	PLEKHA5	ENST00000538714.5	TSL:1	c.457C>T	p.His153Tyr	missense	Exon 6 of 28	ENSP00000439673.1	Q9HAU0-2
	PLEKHA5	ENST00000299275.10	TSL:1	c.457C>T	p.His153Tyr	missense	Exon 6 of 26	ENSP00000299275.6	Q9HAU0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.34		Gain of catalytic residue at K150 (P = 0)
MVP		0.37
MPC		2.0
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.63
gMVP		0.46
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr12-19410391;