10-113755361-G-C

Variant names:

• chr10-113755361-G-C
• rs3981351
• NM_001395068.1:c.28+56G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001193434.2(PLEKHS1):​c.-281G>C variant causes a 5 prime UTR 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: 31)
• Consequence: PLEKHS1 NM_001193434.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193434.2. 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.28+56G>C		intron	N/A	NP_001381997.1	Q5SXH7-6
	PLEKHS1	NM_001193434.2		c.-281G>C		5_prime_UTR	Exon 2 of 13	NP_001180363.1	Q5SXH7-3
	PLEKHS1	NM_001193435.2		c.-85G>C		5_prime_UTR	Exon 2 of 11	NP_001180364.1	Q5SXH7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHS1	ENST00000694986.1	MANE Select	c.28+56G>C		intron	N/A	ENSP00000511629.1	Q5SXH7-6
	PLEKHS1	ENST00000369312.9	TSL:2	c.-281G>C		5_prime_UTR	Exon 2 of 13	ENSP00000358318.4	Q5SXH7-3
	PLEKHS1	ENST00000619563.5	TSL:5	c.-85G>C		5_prime_UTR	Exon 2 of 11	ENSP00000483759.1	Q5SXH7-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.51
PhyloP100		0.049

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3981351;

hg19: chr10-115515120;