Variant chr14-95535103-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016417.3(GLRX5):c.14T>C(p.Leu5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,314,740 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L5L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

GLRX5
NM_016417.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006549865).

BP6

Variant 14-95535103-T-C is Benign according to our data. Variant chr14-95535103-T-C is described in ClinVar as [Benign]. Clinvar id is 1600774.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRX5	NM_016417.3 linkuse as main transcript	c.14T>C	p.Leu5Pro	missense_variant	1/2	ENST00000331334.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRX5	ENST00000331334.5 linkuse as main transcript	c.14T>C	p.Leu5Pro	missense_variant	1/2	1	NM_016417.3	P1
GLRX5	ENST00000553672.1 linkuse as main transcript	n.301+1300T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000337

AC:

AN:

151442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000885

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.000825

AC:

AN:

63064

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

36702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00896

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000182

AC:

212

AN:

1163186

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

102

AN XY:

572030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000518

Gnomad4 ASJ exome

AF:

0.00841

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000176

Gnomad4 FIN exome

AF:

0.0000352

Gnomad4 NFE exome

AF:

0.0000421

Gnomad4 OTH exome

AF:

0.000540

GnomAD4 genome

AF:

0.000337

AC:

AN:

151554

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000885

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.000686

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

Eigen

Benign

0.081

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.3

REVEL

Benign

0.25

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.35

MutPred

0.36

Gain of loop (P = 0.0045);

MVP

0.56

MPC

0.91

ClinPred

0.21

GERP RS

4.6

Varity_R

0.74

gMVP

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over