Variant chr3-114018680-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020817.2(CCDC191):c.1161C>G(p.Asn387Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000412 in 1,456,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCDC191
NM_020817.2 missense, splice_region

Scores

Splicing: ADA: 0.9549

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

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

CCDC191 links:

LOC105374048 (HGNC:):

LOC105374048 links:

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]

QTRT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34629413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC191	NM_020817.2 linkuse as main transcript	c.1161C>G	p.Asn387Lys	missense_variant, splice_region_variant	8/17	ENST00000295878.8	NP_065868.1
LOC105374048	XR_924347.4 linkuse as main transcript	n.3161G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC191	ENST00000295878.8 linkuse as main transcript	c.1161C>G	p.Asn387Lys	missense_variant, splice_region_variant	8/17	1	NM_020817.2	ENSP00000295878	P1	Q8NCU4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456472

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000469

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.1161C>G (p.N387K) alteration is located in exon 8 (coding exon 8) of the CCDC191 gene. This alteration results from a C to G substitution at nucleotide position 1161, causing the asparagine (N) at amino acid position 387 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.77

MutationTaster

Benign

0.83

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.60

T;.

Polyphen

1.0

D;D

Vest4

0.58

MutPred

0.19

Gain of ubiquitination at N387 (P = 0.0051);.;

MVP

0.57

MPC

0.79

ClinPred

0.95

GERP RS

5.8

Varity_R

0.21

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.71

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over