NM_016417.3:c.-16C>T

Variant names:

• chr14-95535074-C-T
• rs554961847
• NM_016417.3:c.-16C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016417.3(GLRX5):​c.-16C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,336,230 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: GLRX5 NM_016417.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 14-95535074-C-T is Benign according to our data. Variant chr14-95535074-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 389476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00265 (403/152062) while in subpopulation AFR AF = 0.00903 (375/41530). AF 95% confidence interval is 0.00828. There are 2 homozygotes in GnomAd4. There are 192 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_057501.2
	GLRX5	NM_016417.3	MANE Select	c.-16C>T		5_prime_UTR	Exon 1 of 2	NP_057501.2
	SNHG10	NR_001459.2		n.-202G>A		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.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000328570.4	Q86SX6
	GLRX5	ENST00000331334.5	TSL:1 MANE Select	c.-16C>T		5_prime_UTR	Exon 1 of 2	ENSP00000328570.4	Q86SX6
	GLRX5	ENST00000902982.1		c.-16C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000573041.1

Frequencies

GnomAD3 genomes AF: 0.00266 AC: 404 AN: 151950 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00908

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000220 AC: 15 AN: 68304 AF XY: 0.000151

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000244 AC: 289 AN: 1184168 Hom.: 2 Cov.: 31 AF XY: 0.000224 AC XY: 131 AN XY: 583978

African (AFR) AF: 0.00980 AC: 229 AN: 23372

American (AMR) AF: 0.000587 AC: 12 AN: 20450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17784

East Asian (EAS) AF: 0.000748 AC: 15 AN: 20042

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 62964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27314

Middle Eastern (MID) AF: 0.000325 AC: 1 AN: 3080

European-Non Finnish (NFE) AF: 0.00000830 AC: 8 AN: 963712

Other (OTH) AF: 0.000506 AC: 23 AN: 45450

GnomAD4 genome AF: 0.00265 AC: 403 AN: 152062 Hom.: 2 Cov.: 33 AF XY: 0.00258 AC XY: 192 AN XY: 74356

African (AFR) AF: 0.00903 AC: 375 AN: 41530

American (AMR) AF: 0.000982 AC: 15 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

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

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67948

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00163 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		-0.41
PromoterAI		0.0057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	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: rs554961847; hg19: chr14-96001411;