3-114036691-T-C

Position:

• chr3-114036691-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020817.2(CCDC191):​c.511A>G​(p.Met171Val) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.982

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 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=0.02791214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC191	NM_020817.2	c.511A>G	p.Met171Val	missense_variant	5/17	ENST00000295878.8	NP_065868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC191	ENST00000295878.8	c.511A>G	p.Met171Val	missense_variant	5/17	1	NM_020817.2	ENSP00000295878	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.511A>G (p.M171V) alteration is located in exon 5 (coding exon 5) of the CCDC191 gene. This alteration results from a A to G substitution at nucleotide position 511, causing the methionine (M) at amino acid position 171 to be replaced by a valine (V). 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	0.072
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.72
DANN	Benign	0.58
DEOGEN2	Benign	0.0015	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.028	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.032
Sift	Benign	0.65	T;T;T
Sift4G	Benign	0.59	T;.;T
Polyphen		0.0	B;B;.
Vest4		0.15
MutPred		0.32		Gain of glycosylation at S168 (P = 0.0522);.;.;
MVP		0.13
MPC		0.21
ClinPred		0.056	T
GERP RS		-6.7
Varity_R		0.045
gMVP		0.061

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-113755538;