NM_016417.3:c.*127G>A

Variant names:

• chr14-95544252-G-A
• rs7120
• NM_016417.3:c.*127G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016417.3(GLRX5):​c.*127G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 746,730 control chromosomes in the GnomAD database, including 94,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16955 hom., cov: 33)
  • Exomes 𝑓: 0.50 (77372 hom.)
• Consequence: GLRX5 NM_016417.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.352
• Publications: 18 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), Orphanet, Genomics England PanelApp
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-95544252-G-A is Benign according to our data. Variant chr14-95544252-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX5	NM_016417.3	c.*127G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000331334.5	NP_057501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX5	ENST00000331334.5	c.*127G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_016417.3	ENSP00000328570.4
GLRX5	ENST00000553672.1	n.607G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
GLRX5	ENST00000557731.1	c.*979G>A		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000451800.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69346 AN: 152018 Hom.: 16958 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.499 AC: 296443 AN: 594594 Hom.: 77372 Cov.: 7 AF XY: 0.494 AC XY: 155581 AN XY: 314812

African (AFR) AF: 0.311 AC: 4945 AN: 15906

American (AMR) AF: 0.299 AC: 9466 AN: 31622

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 10901 AN: 19504

East Asian (EAS) AF: 0.290 AC: 9221 AN: 31814

South Asian (SAS) AF: 0.381 AC: 23283 AN: 61176

European-Finnish (FIN) AF: 0.616 AC: 25465 AN: 41356

Middle Eastern (MID) AF: 0.446 AC: 1095 AN: 2456

European-Non Finnish (NFE) AF: 0.547 AC: 196726 AN: 359466

Other (OTH) AF: 0.490 AC: 15341 AN: 31294

GnomAD4 genome AF: 0.456 AC: 69358 AN: 152136 Hom.: 16955 Cov.: 33 AF XY: 0.455 AC XY: 33845 AN XY: 74374

African (AFR) AF: 0.315 AC: 13087 AN: 41488

American (AMR) AF: 0.380 AC: 5820 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1905 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1351 AN: 5178

South Asian (SAS) AF: 0.379 AC: 1824 AN: 4810

European-Finnish (FIN) AF: 0.623 AC: 6593 AN: 10576

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37037 AN: 67998

Other (OTH) AF: 0.461 AC: 976 AN: 2116

Alfa AF: 0.482 Hom.: 30464

Bravo AF: 0.432

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.4
DANN	Benign	0.85
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7120; hg19: chr14-96010589; COSMIC: COSV58763548;