rs10155047

Positions:

• chr3-114054105-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020817.2(CCDC191):​c.91-470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,378 control chromosomes in the GnomAD database, including 1,026 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1024 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2 hom.)
• Consequence: CCDC191 NM_020817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

Genes affected

CCDC191 (HGNC:29272): (coiled-coil domain containing 191)

QTRT2 (HGNC:25771): (queuine tRNA-ribosyltransferase accessory subunit 2) This gene encodes a subunit of tRNA-guanine transglycosylase. tRNA-guanine transglycosylase is a heterodimeric enzyme complex that plays a critical role in tRNA modification by synthesizing the 7-deazaguanosine queuosine, which is found in tRNAs that code for asparagine, aspartic acid, histidine, and tyrosine. The encoded protein may play a role in the queuosine 5'-monophosphate salvage pathway. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC191	NM_020817.2	c.91-470G>A		intron_variant		ENST00000295878.8	NP_065868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC191	ENST00000295878.8	c.91-470G>A		intron_variant		1	NM_020817.2	ENSP00000295878	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16408 AN: 151998 Hom.: 1018 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.103 AC: 27 AN: 262 Hom.: 2 Cov.: 0 AF XY: 0.0970 AC XY: 13 AN XY: 134

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0891

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.108 AC: 16450 AN: 152116 Hom.: 1024 Cov.: 32 AF XY: 0.107 AC XY: 7992 AN XY: 74360

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.0882

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0972 Hom.: 294

Bravo AF: 0.113

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10155047; hg19: chr3-113772952;