NM_016417.3:c.66T>C

Variant names:

• chr14-95535155-T-C
• NM_016417.3:c.66T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_016417.3(GLRX5):​c.66T>C​(p.Gly22Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLRX5 NM_016417.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25
• Publications: 0 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]

SNHG10 (HGNC:27510): (small nucleolar RNA host gene 10) This gene is small nucleolar RNA host gene 10 and represents a non-protein coding RNA. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-95535155-T-C is Benign according to our data. Variant chr14-95535155-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1936597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.

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.66T>C	p.Gly22Gly	synonymous	Exon 1 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.66T>C	p.Gly22Gly	synonymous	Exon 1 of 2	ENSP00000328570.4	Q86SX6
	GLRX5	ENST00000902982.1		c.66T>C	p.Gly22Gly	synonymous	Exon 1 of 2	ENSP00000573041.1
	GLRX5	ENST00000553672.1	TSL:2	n.301+1352T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1153276 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 560676

African (AFR) AF: 0.00 AC: 0 AN: 23268

American (AMR) AF: 0.00 AC: 0 AN: 11844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15572

East Asian (EAS) AF: 0.00 AC: 0 AN: 25174

South Asian (SAS) AF: 0.00 AC: 0 AN: 38382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3060

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 954246

Other (OTH) AF: 0.00 AC: 0 AN: 45290

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.58
PhyloP100		-1.3
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.6

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

hg19: chr14-96001492;