chr14-95534813-T-A

Position:

• chr14-95534813-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NR_001459.2(SNHG10):​n.60A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 172,458 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (114 hom., cov: 34)
  • Exomes 𝑓: 0.036 (19 hom.)
• Consequence: SNHG10 NR_001459.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.252

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-95534813-T-A is Benign according to our data. Variant chr14-95534813-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 673746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0313 (4762/152196) while in subpopulation NFE AF= 0.0481 (3272/67996). AF 95% confidence interval is 0.0467. There are 114 homozygotes in gnomad4. There are 2204 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 114 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG10	NR_001459.2	n.60A>T		non_coding_transcript_exon_variant	1/2
SNHG10	NR_003138.3	n.60A>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNHG10	ENST00000553559.1	n.60A>T		non_coding_transcript_exon_variant	1/2	3
SNHG10	ENST00000660378.3	n.77A>T		non_coding_transcript_exon_variant	1/2
GLRX5	ENST00000553672.1	n.301+1010T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4767 AN: 152078 Hom.: 114 Cov.: 34

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0359 AC: 727 AN: 20262 Hom.: 19 Cov.: 0 AF XY: 0.0382 AC XY: 431 AN XY: 11284

Gnomad4 AFR exome AF: 0.00870

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0509

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0433

Gnomad4 OTH exome AF: 0.0281

GnomAD4 genome AF: 0.0313 AC: 4762 AN: 152196 Hom.: 114 Cov.: 34 AF XY: 0.0296 AC XY: 2204 AN XY: 74404

Gnomad4 AFR AF: 0.00857

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0481

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0379 Hom.: 24

Bravo AF: 0.0296

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.9
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs45582537; hg19: chr14-96001150;