10-113767352-A-C

Variant names:

• chr10-113767352-A-C
• NM_001395068.1:c.232A>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.232A>C​(p.Ser78Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S78G) has been classified 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: 5.72
• 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=0.1664862).

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.232A>C	p.Ser78Arg	missense	Exon 5 of 13	NP_001381997.1	Q5SXH7-6
	PLEKHS1	NM_182601.2		c.214A>C	p.Ser72Arg	missense	Exon 4 of 12	NP_872407.1	A0A384P5Z2
	PLEKHS1	NM_024889.5		c.232A>C	p.Ser78Arg	missense	Exon 5 of 12	NP_079165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHS1	ENST00000694986.1	MANE Select	c.232A>C	p.Ser78Arg	missense	Exon 5 of 13	ENSP00000511629.1	Q5SXH7-6
	PLEKHS1	ENST00000369310.7	TSL:1	c.214A>C	p.Ser72Arg	missense	Exon 4 of 12	ENSP00000358316.3	Q5SXH7-5
	PLEKHS1	ENST00000361048.6	TSL:2	c.232A>C	p.Ser78Arg	missense	Exon 5 of 12	ENSP00000354332.1	Q5SXH7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.24
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.084
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		5.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.053
Sift	Benign	0.31	T
Sift4G	Benign	0.23	T
Vest4		0.29
MutPred		0.36		Loss of phosphorylation at S72 (P = 0.0634)
MVP		0.16
MPC		0.21
ClinPred		0.38	T
GERP RS		5.8
gMVP		0.28
Mutation Taster		=78/22	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: chr10-115527111;