NM_001395068.1:c.316A>G

Variant names:

• chr10-113767436-A-G
• rs373783132
• NM_001395068.1:c.316A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395068.1(PLEKHS1):​c.316A>G​(p.Ile106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. I106L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: PLEKHS1 NM_001395068.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1381746).

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.316A>G	p.Ile106Val	missense	Exon 5 of 13	NP_001381997.1	Q5SXH7-6
	PLEKHS1	NM_182601.2		c.298A>G	p.Ile100Val	missense	Exon 4 of 12	NP_872407.1	A0A384P5Z2
	PLEKHS1	NM_001193434.2		c.52A>G	p.Ile18Val	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.316A>G	p.Ile106Val	missense	Exon 5 of 13	ENSP00000511629.1	Q5SXH7-6
	PLEKHS1	ENST00000369310.7	TSL:1	c.298A>G	p.Ile100Val	missense	Exon 4 of 12	ENSP00000358316.3	Q5SXH7-5
	PLEKHS1	ENST00000369312.9	TSL:2	c.52A>G	p.Ile18Val	missense	Exon 5 of 13	ENSP00000358318.4	Q5SXH7-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000799 AC: 20 AN: 250404 AF XY: 0.0000813

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461176 Hom.: 0 Cov.: 30 AF XY: 0.0000537 AC XY: 39 AN XY: 726886

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.000650 AC: 56 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111722

Other (OTH) AF: 0.0000497 AC: 3 AN: 60350

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74508

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.17
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	0.15
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.83	T
PhyloP100		1.7
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.18
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0	D
Vest4		0.40
MutPred		0.58		Loss of sheet (P = 0.1158)
MVP		0.14
MPC		0.53
ClinPred		0.30	T
GERP RS		3.4
gMVP		0.26
Mutation Taster		=87/13	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: rs373783132; hg19: chr10-115527195;