3-114050250-G-T

Position:

• chr3-114050250-G-T

Variant summary

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

The NM_020817.2(CCDC191):​c.129+3347C>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 152,268 control chromosomes in the GnomAD database, including 1,015 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 (1015 hom., cov: 32)
• Consequence: CCDC191 NM_020817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC191	NM_020817.2	c.129+3347C>A		intron_variant		ENST00000295878.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC191	ENST00000295878.8	c.129+3347C>A		intron_variant		1	NM_020817.2	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16362 AN: 152150 Hom.: 1009 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0960

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16404 AN: 152268 Hom.: 1015 Cov.: 32 AF XY: 0.107 AC XY: 7965 AN XY: 74446

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0917 Hom.: 689

Bravo AF: 0.112

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	-1.0
CADD	Benign	0.051
DANN	Benign	0.34

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: rs9859901; hg19: chr3-113769097;