NM_001197026.2:c.557C>T

Variant names:

• chr7-30049342-C-T
• rs1792222189
• NM_001197026.2:c.557C>T

Variant summary

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

The NM_001197026.2(PLEKHA8):​c.557C>T​(p.Pro186Leu) 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: PLEKHA8 NM_001197026.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

Genes affected

PLEKHA8 (HGNC:30037): (pleckstrin homology domain containing A8) Enables several functions, including ceramide binding activity; glycolipid transfer activity; and phosphatidylinositol-4-phosphate binding activity. Involved in ER to Golgi ceramide transport. Located in nucleoplasm and trans-Golgi network. [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_001197026.2. 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
	PLEKHA8	NM_001197026.2	MANE Select	c.557C>T	p.Pro186Leu	missense	Exon 5 of 14	NP_001183955.1	A0A2P1JJM6
	PLEKHA8	NM_001197027.2		c.557C>T	p.Pro186Leu	missense	Exon 5 of 14	NP_001183956.1	A0A087X1S6
	PLEKHA8	NM_001350973.2		c.557C>T	p.Pro186Leu	missense	Exon 5 of 14	NP_001337902.1	Q96JA3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA8	ENST00000449726.6	TSL:1 MANE Select	c.557C>T	p.Pro186Leu	missense	Exon 5 of 14	ENSP00000397947.1	Q96JA3-1
	PLEKHA8	ENST00000440706.3	TSL:1	c.557C>T	p.Pro186Leu	missense	Exon 5 of 14	ENSP00000407802.2	Q96JA3-1
	PLEKHA8	ENST00000396257.6	TSL:1	c.557C>T	p.Pro186Leu	missense	Exon 5 of 14	ENSP00000379556.2	Q96JA3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.15
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.35	T
PhyloP100		7.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.44		Loss of glycosylation at P186 (P = 0.0127)
MVP		0.65
MPC		0.99
ClinPred		0.95	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.57
Mutation Taster		=38/62	disease causing

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

dbSNP: rs1792222189; hg19: chr7-30088958;