14-95544252-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016417.3(GLRX5):​c.*127G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000336 in 595,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GLRX5 NM_016417.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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), 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.*127G>T		3_prime_UTR	Exon 2 of 2	NP_057501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX5	ENST00000331334.5	TSL:1 MANE Select	c.*127G>T		3_prime_UTR	Exon 2 of 2	ENSP00000328570.4	Q86SX6
	GLRX5	ENST00000902982.1		c.*127G>T		3_prime_UTR	Exon 2 of 2	ENSP00000573041.1
	GLRX5	ENST00000557731.1	TSL:5	c.*979G>T		3_prime_UTR	Exon 2 of 2	ENSP00000451800.1	H0YJM6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000336 AC: 2 AN: 595156 Hom.: 0 Cov.: 7 AF XY: 0.00000635 AC XY: 2 AN XY: 315078

African (AFR) AF: 0.00 AC: 0 AN: 15910

American (AMR) AF: 0.00 AC: 0 AN: 31644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19526

East Asian (EAS) AF: 0.00 AC: 0 AN: 31820

South Asian (SAS) AF: 0.00 AC: 0 AN: 61210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2456

European-Non Finnish (NFE) AF: 0.00000556 AC: 2 AN: 359890

Other (OTH) AF: 0.00 AC: 0 AN: 31316

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 30464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.83
PhyloP100		-0.35

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;