rs61741379

Variant names:

• chr1-6473333-G-A
• NM_020631.6:c.713C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-6473333-G-A
• chr1-6473333-G-C
• chr1-6473333-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020631.6(PLEKHG5):​c.713C>T​(p.Thr238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T238S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PLEKHG5 NM_020631.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054540485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG5	NM_020631.6	c.713C>T	p.Thr238Ile	missense_variant	Exon 8 of 21	ENST00000377728.8	NP_065682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG5	ENST00000377728.8	c.713C>T	p.Thr238Ile	missense_variant	Exon 8 of 21	2	NM_020631.6	ENSP00000366957.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406160 Hom.: 0 Cov.: 36 AF XY: 0.00000144 AC XY: 1 AN XY: 694592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.77
DEOGEN2	Benign	0.15	.;.;.;.;.;.;.;.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.35	T;.;T;T;T;T;.;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.055	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	.;.;.;.;.;.;.;.;N;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.80	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.044
Sift	Benign	0.25	T;T;T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.050	T;D;D;D;D;D;D;D;D;D
Polyphen		0.0	.;.;.;.;B;B;.;.;B;B
Vest4		0.068
MutPred		0.20		.;.;.;.;.;.;.;.;Loss of relative solvent accessibility (P = 0.0071);.;
MVP		0.10
MPC		0.28
ClinPred		0.98	D
GERP RS		0.98
Varity_R		0.042
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-6533393;