16-67286320-GC-AT

Variant names:

• chr16-67286320-GC-AT
• NM_001129729.3:c.2489_2490delGCinsAT
• PLEKHG4 p.Arg830His

Variant summary

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

The NM_001129729.3(PLEKHG4):​c.2489_2490delGCinsAT​(p.Arg830His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00000398 in 1 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: GnomAD MNV: 𝑓 0.0000040 Genomes: not found (cov: 33)
• Consequence: PLEKHG4 NM_001129729.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

Genes affected

PLEKHG4 (HGNC:24501): (pleckstrin homology and RhoGEF domain containing G4) The protein encoded by this gene can function as a guanine nucleotide exchange factor (GEF) and may play a role in intracellular signaling and cytoskeleton dynamics at the Golgi apparatus. Polymorphisms in the region of this gene have been found to be associated with spinocerebellar ataxia in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129729.3. 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
	PLEKHG4	NM_001129729.3	MANE Select	c.2489_2490delGCinsAT	p.Arg830His	missense	N/A	NP_001123201.1	A0A024R6X4
	PLEKHG4	NM_001129727.3		c.2489_2490delGCinsAT	p.Arg830His	missense	N/A	NP_001123199.1	Q58EX7-1
	PLEKHG4	NM_001129728.2		c.2489_2490delGCinsAT	p.Arg830His	missense	N/A	NP_001123200.1	A0A024R6X4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG4	ENST00000379344.8	TSL:1 MANE Select	c.2489_2490delGCinsAT	p.Arg830His	missense	N/A	ENSP00000368649.3	Q58EX7-1
	PLEKHG4	ENST00000450733.5	TSL:1	c.2246_2247delGCinsAT	p.Arg749His	missense	N/A	ENSP00000398030.1	Q58EX7-2
	PLEKHG4	ENST00000393966.1	TSL:1	n.*1198+1863_*1198+1864delGCinsAT		intron	N/A	ENSP00000462601.1	Q58EX7-3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.00000398 AC: 1 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

hg19: chr16-67320223;