rs1224886992

Variant names:

• chr10-113766463-T-A
• rs1224886992
• NM_001395068.1:c.81T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113766463-T-A
• chr10-113766463-T-C

Variant summary

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

The NM_001395068.1(PLEKHS1):​c.81T>A​(p.Phe27Leu) 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. 12/20 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: PLEKHS1 NM_001395068.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.364
• Publications: 0 publications found

Genes affected

PLEKHS1 (HGNC:26285): (pleckstrin homology domain containing S1)

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=0.12918451).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395068.1. 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
	PLEKHS1	NM_001395068.1	MANE Select	c.81T>A	p.Phe27Leu	missense	Exon 3 of 13	NP_001381997.1	Q5SXH7-6
	PLEKHS1	NM_182601.2		c.63T>A	p.Phe21Leu	missense	Exon 2 of 12	NP_872407.1	A0A384P5Z2
	PLEKHS1	NM_024889.5		c.81T>A	p.Phe27Leu	missense	Exon 3 of 12	NP_079165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHS1	ENST00000694986.1	MANE Select	c.81T>A	p.Phe27Leu	missense	Exon 3 of 13	ENSP00000511629.1	Q5SXH7-6
	PLEKHS1	ENST00000369310.7	TSL:1	c.63T>A	p.Phe21Leu	missense	Exon 2 of 12	ENSP00000358316.3	Q5SXH7-5
	PLEKHS1	ENST00000361048.6	TSL:2	c.81T>A	p.Phe27Leu	missense	Exon 3 of 12	ENSP00000354332.1	Q5SXH7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.91
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.36
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.25
Sift	Benign	0.56	T
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MutPred		0.62		Gain of ubiquitination at K23 (P = 0.0701)
MVP		0.16
MPC		0.74
ClinPred		0.77	D
GERP RS		1.9
gMVP		0.30
Mutation Taster		=91/9	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

dbSNP: rs1224886992; hg19: chr10-115526222;