14-95541473-C-T

Variant names:

• chr14-95541473-C-T
• rs1007813
• NM_016417.3:c.296-2474C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016417.3(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 NM_016417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• sideroblastic anemia 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• spasticity-ataxia-gait anomalies syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX5	NM_016417.3	MANE Select	c.296-2474C>T		intron	N/A	NP_057501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX5	ENST00000331334.5	TSL:1 MANE Select	c.296-2474C>T		intron	N/A	ENSP00000328570.4	Q86SX6
	GLRX5	ENST00000902982.1		c.296-2483C>T		intron	N/A	ENSP00000573041.1
	GLRX5	ENST00000557731.1	TSL:5	c.111-1500C>T		intron	N/A	ENSP00000451800.1	H0YJM6

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

African (AFR) AF: 0.207 AC: 8588 AN: 41510

American (AMR) AF: 0.269 AC: 4119 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1132 AN: 5186

South Asian (SAS) AF: 0.381 AC: 1839 AN: 4828

European-Finnish (FIN) AF: 0.428 AC: 4529 AN: 10570

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27512 AN: 68010

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.379 Hom.: 19137

Bravo AF: 0.314

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.62
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1007813; hg19: chr14-96007810;