10-113767463-C-T

Variant names:

• chr10-113767463-C-T
• rs1489678048
• NM_001395068.1:c.343C>T

Variant summary

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

The NM_001395068.1(PLEKHS1):​c.343C>T​(p.Leu115Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,288 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: PLEKHS1 NM_001395068.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

Genes affected

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

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_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.343C>T	p.Leu115Phe	missense	Exon 5 of 13	NP_001381997.1	Q5SXH7-6
	PLEKHS1	NM_182601.2		c.325C>T	p.Leu109Phe	missense	Exon 4 of 12	NP_872407.1	A0A384P5Z2
	PLEKHS1	NM_001193434.2		c.79C>T	p.Leu27Phe	missense	Exon 5 of 13	NP_001180363.1	Q5SXH7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHS1	ENST00000694986.1	MANE Select	c.343C>T	p.Leu115Phe	missense	Exon 5 of 13	ENSP00000511629.1	Q5SXH7-6
	PLEKHS1	ENST00000369310.7	TSL:1	c.325C>T	p.Leu109Phe	missense	Exon 4 of 12	ENSP00000358316.3	Q5SXH7-5
	PLEKHS1	ENST00000369312.9	TSL:2	c.79C>T	p.Leu27Phe	missense	Exon 5 of 13	ENSP00000358318.4	Q5SXH7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248344 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1459288 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 725840

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111068

Other (OTH) AF: 0.0000166 AC: 1 AN: 60290

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000597

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	0.67
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.87	T
PhyloP100		3.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.31
Sift	Benign	0.045	D
Sift4G	Pathogenic	0.0	D
Vest4		0.57
MutPred		0.67		Loss of catalytic residue at L109 (P = 0.1115)
MVP		0.27
MPC		0.72
ClinPred		0.96	D
GERP RS		5.8
gMVP		0.72
Mutation Taster		=71/29	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

dbSNP: rs1489678048; hg19: chr10-115527222;