Genetic Variant NM_016417.3:c.28G>C (chr14-95535117-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016417.3(GLRX5):c.28G>C(p.Ala10Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000346 in 1,156,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

GLRX5
NM_016417.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.322705).

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>C	p.Ala10Pro	missense	Exon 1 of 2	NP_057501.2
SNHG10	NR_001459.2		n.-245C>G		upstream_gene	N/A
SNHG10	NR_003138.3		n.-245C>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.28G>C	p.Ala10Pro	missense	Exon 1 of 2	ENSP00000328570.4	Q86SX6
GLRX5	ENST00000902982.1		c.28G>C	p.Ala10Pro	missense	Exon 1 of 2	ENSP00000573041.1
GLRX5	ENST00000553672.1	TSL:2	n.301+1314G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1156880

Hom.:

Cov.:

AF XY:

0.00000176

AC XY:

AN XY:

567606

show subpopulations

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:

0.000148

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:

0.0000226

AC:

AN:

44302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Benign

0.072

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

5.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.88

REVEL

Benign

0.065

Sift

Uncertain

0.014

Sift4G

Benign

0.089

Polyphen

0.80

Vest4

0.41

MutPred

0.46

Gain of glycosylation at A10 (P = 0.0406)

MVP

0.32

MPC

0.73

ClinPred

0.88

GERP RS

3.7

PromoterAI

0.025

Neutral

(source)

Varity_R

0.63

gMVP

0.64

Mutation Taster

=86/14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over