Genetic Variant GLRX5:p.Ala9Pro (chr14-95535114-G-C) – 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.25G>C(p.Ala9Pro) 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. 14/22 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. A9T) 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: 1.59

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=0.17033711).

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.25G>C	p.Ala9Pro	missense	Exon 1 of 2	NP_057501.2
SNHG10	NR_001459.2		n.-242C>G		upstream_gene	N/A
SNHG10	NR_003138.3		n.-242C>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX5	ENST00000331334.5	TSL:1 MANE Select	c.25G>C	p.Ala9Pro	missense	Exon 1 of 2	ENSP00000328570.4	Q86SX6
GLRX5	ENST00000902982.1		c.25G>C	p.Ala9Pro	missense	Exon 1 of 2	ENSP00000573041.1
GLRX5	ENST00000553672.1	TSL:2	n.301+1311G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

57334

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1156522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

567682

African (AFR)

AF:

0.00

AC:

AN:

23074

American (AMR)

AF:

0.00

AC:

AN:

18364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16762

East Asian (EAS)

AF:

0.00

AC:

AN:

20020

South Asian (SAS)

AF:

0.00

AC:

AN:

53552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3000

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

947818

Other (OTH)

AF:

0.00

AC:

AN:

44208

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.67

M_CAP

Benign

0.040

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.48

REVEL

Benign

0.076

Sift

Benign

0.16

Sift4G

Benign

0.12

Polyphen

0.38

Vest4

0.25

MutPred

0.40

Loss of helix (P = 0.0072)

MVP

0.44

MPC

0.73

ClinPred

0.51

GERP RS

3.6

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.21

gMVP

0.84

Mutation Taster

=64/36

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

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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