14-95535109-G-C

Variant names:

• chr14-95535109-G-C
• rs1388603479
• NM_016417.3:c.20G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016417.3(GLRX5):​c.20G>C​(p.Arg7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000305 in 1,312,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: GLRX5 NM_016417.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16234395).

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.20G>C	p.Arg7Pro	missense	Exon 1 of 2	NP_057501.2
	SNHG10	NR_001459.2		n.-237C>G		upstream_gene	N/A
	SNHG10	NR_003138.3		n.-237C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX5	ENST00000331334.5	TSL:1 MANE Select	c.20G>C	p.Arg7Pro	missense	Exon 1 of 2	ENSP00000328570.4	Q86SX6
	GLRX5	ENST00000902982.1		c.20G>C	p.Arg7Pro	missense	Exon 1 of 2	ENSP00000573041.1
	GLRX5	ENST00000553672.1	TSL:2	n.301+1306G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151598 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000172 AC: 2 AN: 1160786 Hom.: 0 Cov.: 31 AF XY: 0.00000175 AC XY: 1 AN XY: 570410

African (AFR) AF: 0.0000432 AC: 1 AN: 23128

American (AMR) AF: 0.00 AC: 0 AN: 18818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16946

East Asian (EAS) AF: 0.00 AC: 0 AN: 19878

South Asian (SAS) AF: 0.00 AC: 0 AN: 55438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3006

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 949836

Other (OTH) AF: 0.00 AC: 0 AN: 44358

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151706 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74164

African (AFR) AF: 0.0000482 AC: 2 AN: 41504

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67874

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.094
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.12	T
Polyphen		0.0060	B
Vest4		0.26
MutPred		0.46		Loss of MoRF binding (P = 2e-04)
MVP		0.31
MPC		0.82
ClinPred		0.72	D
GERP RS		4.6
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.66
Mutation Taster		=66/34	polymorphism

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: rs1388603479; hg19: chr14-96001446;