NM_020631.6:c.1800+107C>A

Variant names:

• chr1-6470129-G-T
• rs3007421
• NM_020631.6:c.1800+107C>A

Variant summary

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

The NM_020631.6(PLEKHG5):​c.1800+107C>A variant causes a intron 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLEKHG5 NM_020631.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.956
• Publications: 36 publications found

Genes affected

PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

PLEKHG5 Gene-Disease associations (from GenCC):

• neuromuscular disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease recessive intermediate C

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• neuronopathy, distal hereditary motor, autosomal recessive 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020631.6. 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
	PLEKHG5	NM_020631.6	MANE Select	c.1800+107C>A		intron	N/A	NP_065682.2
	PLEKHG5	NM_001265593.2		c.2007+107C>A		intron	N/A	NP_001252522.1	A0A804EMX3
	PLEKHG5	NM_001042663.3		c.1911+107C>A		intron	N/A	NP_001036128.2	O94827-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG5	ENST00000377728.8	TSL:2 MANE Select	c.1800+107C>A		intron	N/A	ENSP00000366957.3	O94827-5
	PLEKHG5	ENST00000377732.5	TSL:1	c.1911+107C>A		intron	N/A	ENSP00000366961.1	O94827-3
	PLEKHG5	ENST00000400915.8	TSL:1	c.1911+107C>A		intron	N/A	ENSP00000383706.4	O94827-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1107372 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 557680

African (AFR) AF: 0.00 AC: 0 AN: 25916

American (AMR) AF: 0.00 AC: 0 AN: 36072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20260

East Asian (EAS) AF: 0.00 AC: 0 AN: 37772

South Asian (SAS) AF: 0.00 AC: 0 AN: 69948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 823916

Other (OTH) AF: 0.00 AC: 0 AN: 48176

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2019

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.57
PhyloP100		0.96

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: rs3007421; hg19: chr1-6530189;