rs375714975

Variant names:

• chr14-95535130-G-A
• NM_016417.3:c.41G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-95535130-G-A
• chr14-95535130-G-C
• chr14-95535130-G-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.41G>A​(p.Arg14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000916 in 1,091,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 9.2e-7 (0 hom.)
• Consequence: GLRX5 NM_016417.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

SNHG10 (HGNC:27510): (small nucleolar RNA host gene 10) This gene is small nucleolar RNA host gene 10 and represents a non-protein coding RNA. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

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=0.16053891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX5	NM_016417.3	c.41G>A	p.Arg14His	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.41G>A	p.Arg14His	missense_variant	Exon 1 of 2	1	NM_016417.3	ENSP00000328570.4
GLRX5	ENST00000553672.1	n.301+1327G>A		intron_variant	Intron 1 of 1	2
GLRX5	ENST00000557731.1	c.-145G>A		upstream_gene_variant		5		ENSP00000451800.1
SNHG10	ENST00000660378.3	n.-241C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1091166 Hom.: 0 Cov.: 31 AF XY: 0.00000189 AC XY: 1 AN XY: 528258

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: 0.00000109

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.042
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.067
Sift	Benign	0.047	D
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.52		Loss of methylation at R14 (P = 0.0285);
MVP		0.26
MPC		0.70
ClinPred		0.72	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.62

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: chr14-96001467;