11-119193159-C-A

Variant summary

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

The NM_001145018.3(DRC12):​c.341G>T​(p.Gly114Val) 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. 15/21 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

DRC12
NM_001145018.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02
Variant links:
Genes affected
DRC12 (HGNC:27446): (dynein regulatory complex subunit 12 homolog) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.054204315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRC12NM_001145018.3 linkc.341G>T p.Gly114Val missense_variant Exon 5 of 7 ENST00000503566.7 NP_001138490.1 Q494R4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC153ENST00000503566.7 linkc.341G>T p.Gly114Val missense_variant Exon 5 of 7 5 NM_001145018.3 ENSP00000423567.2 Q494R4-1
CCDC153ENST00000415318.2 linkc.341G>T p.Gly114Val missense_variant Exon 6 of 8 5 ENSP00000445431.1 Q494R4-1
CCDC153ENST00000375140.7 linkn.1359G>T non_coding_transcript_exon_variant Exon 5 of 7 5

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.341G>T (p.G114V) alteration is located in exon 5 (coding exon 4) of the CCDC153 gene. This alteration results from a G to T substitution at nucleotide position 341, causing the glycine (G) at amino acid position 114 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
0.10
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
9.9
DANN
Benign
0.62
DEOGEN2
Benign
0.0030
T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.48
.;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.038
Sift
Benign
0.055
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.0
B;B
Vest4
0.11
MutPred
0.16
Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP
0.12
MPC
0.17
ClinPred
0.034
T
GERP RS
1.1
Varity_R
0.055
gMVP
0.089

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: chr11-119063869; API