Variant 14-95535073-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_016417.3(GLRX5):c.-17C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,337,898 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 16 hom. )

Consequence

GLRX5
NM_016417.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.821

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 14-95535073-C-A is Benign according to our data. Variant chr14-95535073-C-A is described in ClinVar as [Benign]. Clinvar id is 381201.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00303 (460/152046) while in subpopulation NFE AF= 0.00449 (305/67948). AF 95% confidence interval is 0.00407. There are 2 homozygotes in gnomad4. There are 228 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRX5	NM_016417.3 linkuse as main transcript	c.-17C>A		5_prime_UTR_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.-17C>A		5_prime_UTR_variant	1/2	1	NM_016417.3	P1
GLRX5	ENST00000553672.1 linkuse as main transcript	n.301+1270C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

460

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00474

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00449

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00366

AC:

250

AN:

68320

Hom.:

AF XY:

0.00358

AC XY:

142

AN XY:

39668

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00674

Gnomad NFE exome

AF:

0.00421

Gnomad OTH exome

AF:

0.00301

GnomAD4 exome

AF:

0.00392

AC:

4653

AN:

1185852

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2225

AN XY:

584734

show subpopulations

Gnomad4 AFR exome

AF:

0.000470

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.00681

Gnomad4 NFE exome

AF:

0.00416

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00303

AC:

460

AN:

152046

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

228

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00474

Gnomad4 NFE

AF:

0.00449

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.00271

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 15, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.3

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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