1-6492439-T-G

Variant names:

• chr1-6492439-T-G
• rs9434795
• ENST00000377732.5:c.24+4054A>C

Variant summary

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

The NM_001042663.3(PLEKHG5):​c.24+4054A>C 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: 32)
• Consequence: PLEKHG5 NM_001042663.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 8 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• neuronopathy, distal hereditary motor, autosomal recessive 4

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

ENSG00000299237 (HGNC:):

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_001042663.3. 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
	PLEKHG5	NM_001042663.3		c.24+4054A>C		intron	N/A	NP_001036128.2
	PLEKHG5	NM_001265592.2		c.24+4054A>C		intron	N/A	NP_001252521.2
	PLEKHG5	NM_198681.4		c.-88+4054A>C		intron	N/A	NP_941374.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG5	ENST00000377732.5	TSL:1	c.24+4054A>C		intron	N/A	ENSP00000366961.1
	PLEKHG5	ENST00000400915.8	TSL:1	c.24+4054A>C		intron	N/A	ENSP00000383706.4
	PLEKHG5	ENST00000377740.5	TSL:1	c.-88+4054A>C		intron	N/A	ENSP00000366969.4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.46
PhyloP100		-0.067

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9434795; hg19: chr1-6552499;