10-113766689-T-C

Variant names:

• chr10-113766689-T-C
• rs372022414
• NM_001395068.1:c.195T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001395068.1(PLEKHS1):​c.195T>C​(p.His65His) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLEKHS1 NM_001395068.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.01 with no splicing effect.

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.195T>C	p.His65His	synonymous	Exon 4 of 13	NP_001381997.1	Q5SXH7-6
	PLEKHS1	NM_182601.2		c.177T>C	p.His59His	synonymous	Exon 3 of 12	NP_872407.1	A0A384P5Z2
	PLEKHS1	NM_024889.5		c.195T>C	p.His65His	synonymous	Exon 4 of 12	NP_079165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHS1	ENST00000694986.1	MANE Select	c.195T>C	p.His65His	synonymous	Exon 4 of 13	ENSP00000511629.1	Q5SXH7-6
	PLEKHS1	ENST00000369310.7	TSL:1	c.177T>C	p.His59His	synonymous	Exon 3 of 12	ENSP00000358316.3	Q5SXH7-5
	PLEKHS1	ENST00000361048.6	TSL:2	c.195T>C	p.His65His	synonymous	Exon 4 of 12	ENSP00000354332.1	Q5SXH7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.2
DANN	Benign	0.23
PhyloP100		-0.010

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: rs372022414; hg19: chr10-115526448;