Genetic Variant GLRX5:p.Ala10Thr (chr14-95535117-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016417.3(GLRX5):c.28G>A(p.Ala10Thr) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLRX5
NM_016417.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.60

Publications

0 publications found

Variant links:

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]

GLRX5 links:

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]

SNHG10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18848878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016417.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GLRX5	NM_016417.3	MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 2	NP_057501.2
SNHG10	NR_001459.2		n.-245C>T		upstream_gene	N/A
SNHG10	NR_003138.3		n.-245C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX5	ENST00000331334.5	TSL:1 MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 2	ENSP00000328570.4	Q86SX6
GLRX5	ENST00000902982.1		c.28G>A	p.Ala10Thr	missense	Exon 1 of 2	ENSP00000573041.1
GLRX5	ENST00000553672.1	TSL:2	n.301+1314G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1156880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

567606

African (AFR)

AF:

0.00

AC:

AN:

23086

American (AMR)

AF:

0.00

AC:

AN:

18268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16732

East Asian (EAS)

AF:

0.00

AC:

AN:

20216

South Asian (SAS)

AF:

0.00

AC:

AN:

53122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3004

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

947886

Other (OTH)

AF:

0.00

AC:

AN:

44302

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

5.6

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.22

REVEL

Benign

0.045

Sift

Uncertain

0.012

Sift4G

Benign

0.15

Polyphen

0.15

Vest4

0.27

MutPred

0.43

Gain of relative solvent accessibility (P = 0.09)

MVP

0.27

MPC

0.55

ClinPred

0.67

GERP RS

3.7

PromoterAI

-0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.14

gMVP

0.52

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over