14-95535156-G-T

Variant names:

• chr14-95535156-G-T
• NM_016417.3:c.67G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016417.3(GLRX5):​c.67G>T​(p.Gly23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000865 in 1,156,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: GLRX5 NM_016417.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

Genes affected

GLRX5 (HGNC:20134): (glutaredoxin 5) This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19524142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX5	NM_016417.3	c.67G>T	p.Gly23Cys	missense_variant	Exon 1 of 2	ENST00000331334.5	NP_057501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX5	ENST00000331334.5	c.67G>T	p.Gly23Cys	missense_variant	Exon 1 of 2	1	NM_016417.3	ENSP00000328570.4
GLRX5	ENST00000553672.1	n.301+1353G>T		intron_variant	Intron 1 of 1	2
GLRX5	ENST00000557731.1	c.-119G>T		upstream_gene_variant		5		ENSP00000451800.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.65e-7 AC: 1 AN: 1156662 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 562300

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000818

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.14
Sift	Benign	0.030	D
Sift4G	Uncertain	0.027	D
Polyphen		0.70	P
Vest4		0.29
MutPred		0.44		Gain of sheet (P = 0.0266);
MVP		0.39
MPC		0.60
ClinPred		0.63	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.0
Varity_R		0.14
gMVP		0.42

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: chr14-96001493;