Genetic Variant NM_016417.3:c.25G>A (chr14-95535114-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.25G>A(p.Ala9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000605 in 1,156,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000061 ( 0 hom. )

Consequence

GLRX5
NM_016417.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

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=0.1171543).

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>A	p.Ala9Thr	missense	Exon 1 of 2	NP_057501.2
SNHG10	NR_001459.2		n.-242C>T		upstream_gene	N/A
SNHG10	NR_003138.3		n.-242C>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.25G>A	p.Ala9Thr	missense	Exon 1 of 2	ENSP00000328570.4	Q86SX6
GLRX5	ENST00000902982.1		c.25G>A	p.Ala9Thr	missense	Exon 1 of 2	ENSP00000573041.1
GLRX5	ENST00000553672.1	TSL:2	n.301+1311G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000605

AC:

AN:

1156522

Hom.:

Cov.:

AF XY:

0.00000352

AC XY:

AN XY:

567682

show subpopulations

African (AFR)

AF:

0.000217

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:

0.0000452

AC:

AN:

44208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.042

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.72

M_CAP

Benign

0.034

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.6

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.030

REVEL

Benign

0.069

Sift

Benign

0.65

Sift4G

Benign

0.87

Polyphen

0.041

Vest4

0.19

MutPred

0.41

Gain of catalytic residue at A9 (P = 0.0228)

MVP

0.47

MPC

0.55

ClinPred

0.38

GERP RS

3.6

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.075

gMVP

0.74

Mutation Taster

=82/18

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over