rs17180090

Variant names:

• chr14-64724195-C-T
• rs17180090
• NM_001308147.2:c.-39-3398C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308147.2(PLEKHG3):​c.-39-3398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,816 control chromosomes in the GnomAD database, including 1,867 homozygotes. 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: 𝑓 0.15 (1867 hom., cov: 30)
• Consequence: PLEKHG3 NM_001308147.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 16 publications found

Genes affected

PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308147.2. 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
	PLEKHG3	NM_001308147.2	MANE Select	c.-39-3398C>T		intron	N/A	NP_001295076.1	A1L390-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG3	ENST00000247226.13	TSL:1 MANE Select	c.-39-3398C>T		intron	N/A	ENSP00000247226.8	A1L390-1
	PLEKHG3	ENST00000634379.2	TSL:1	c.25-3398C>T		intron	N/A	ENSP00000489373.2	A0A0U1RR71
	PLEKHG3	ENST00000864151.1		c.-39-3398C>T		intron	N/A	ENSP00000534210.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23180 AN: 151698 Hom.: 1864 Cov.: 30

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23210 AN: 151816 Hom.: 1867 Cov.: 30 AF XY: 0.152 AC XY: 11263 AN XY: 74212

African (AFR) AF: 0.190 AC: 7862 AN: 41348

American (AMR) AF: 0.109 AC: 1670 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3466

East Asian (EAS) AF: 0.0258 AC: 133 AN: 5156

South Asian (SAS) AF: 0.159 AC: 763 AN: 4786

European-Finnish (FIN) AF: 0.158 AC: 1666 AN: 10572

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10133 AN: 67906

Other (OTH) AF: 0.151 AC: 318 AN: 2106

Alfa AF: 0.151 Hom.: 3007

Bravo AF: 0.148

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.80
PhyloP100		-0.42
PromoterAI		-0.0023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs17180090; hg19: chr14-65190913;