chr3-114056387-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020817.2(CCDC191):​c.80C>T​(p.Pro27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CCDC191
NM_020817.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043358445).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCDC191NM_020817.2 linkuse as main transcriptc.80C>T p.Pro27Leu missense_variant 1/17 ENST00000295878.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC191ENST00000295878.8 linkuse as main transcriptc.80C>T p.Pro27Leu missense_variant 1/171 NM_020817.2 P1Q8NCU4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsNov 09, 2023The c.80C>T (p.P27L) alteration is located in exon 1 (coding exon 1) of the CCDC191 gene. This alteration results from a C to T substitution at nucleotide position 80, causing the proline (P) at amino acid position 27 to be replaced by a leucine (L). 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
Benign
0.096
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Benign
0.0017
T;T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.011
Sift
Benign
0.97
T;T
Sift4G
Benign
1.0
T;.
Polyphen
0.11
B;B
Vest4
0.20
MutPred
0.27
Loss of glycosylation at P29 (P = 0.0049);Loss of glycosylation at P29 (P = 0.0049);
MVP
0.20
MPC
0.22
ClinPred
0.16
T
GERP RS
2.3
Varity_R
0.035
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-113775234; API