14-95541473-C-T

Position:

• chr14-95541473-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000331334.5(GLRX5):​c.296-2474C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,180 control chromosomes in the GnomAD database, including 9,210 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9210 hom., cov: 33)
• Consequence: GLRX5 ENST00000331334.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRX5	NM_016417.3	c.296-2474C>T		intron_variant		ENST00000331334.5	NP_057501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX5	ENST00000331334.5	c.296-2474C>T		intron_variant		1	NM_016417.3	ENSP00000328570	P1
GLRX5	ENST00000557731.1	c.112-1500C>T		intron_variant		5		ENSP00000451800
GLRX5	ENST00000553672.1	n.302-2474C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50563 AN: 152062 Hom.: 9213 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.332 AC: 50561 AN: 152180 Hom.: 9210 Cov.: 33 AF XY: 0.331 AC XY: 24644 AN XY: 74394

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.330

Alfa AF: 0.384 Hom.: 15603

Bravo AF: 0.314

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs1007813; hg19: chr14-96007810;