14-95535121-C-A

Variant names:

• chr14-95535121-C-A
• rs1390109139
• NM_016417.3:c.32C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016417.3(GLRX5):​c.32C>A​(p.Ala11Asp) variant causes a missense 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. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLRX5 NM_016417.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38555443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX5	NM_016417.3	c.32C>A	p.Ala11Asp	missense_variant	Exon 1 of 2	ENST00000331334.5	NP_057501.2
SNHG10	NR_001459.2	n.-249G>T		upstream_gene_variant
SNHG10	NR_003138.3	n.-249G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX5	ENST00000331334.5	c.32C>A	p.Ala11Asp	missense_variant	Exon 1 of 2	1	NM_016417.3	ENSP00000328570.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1120414 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 546286

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.13
Sift	Benign	0.062	T
Sift4G	Uncertain	0.042	D
Polyphen		0.92	P
Vest4		0.54
MutPred		0.43		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.35
MPC		0.85
ClinPred		0.44	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs1390109139; hg19: chr14-96001458;