11-32602839-G-C

Variant summary

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

The NM_001008391.4(CCDC73):ā€‹c.3212C>Gā€‹(p.Thr1071Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,601,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CCDC73
NM_001008391.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
Variant links:
Genes affected
CCDC73 (HGNC:23261): (coiled-coil domain containing 73)
EIF3M (HGNC:24460): (eukaryotic translation initiation factor 3 subunit M) This gene encodes a protein that is part of the eurkaryotic translation initiation factor 3 complete (eIF-3) required for protein synthesis. Elevated levels of the encoded protein are present in cancer cell lines. Inactivation of the encoded protein has been shown to interfere with translation of herpes virus mRNAs by preventing the association of mRNAs with the ribosomes. A pseudogene of this gene is located on the X chromosome. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

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=0.037080497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC73NM_001008391.4 linkuse as main transcriptc.3212C>G p.Thr1071Arg missense_variant 18/18 ENST00000335185.10 NP_001008392.2 Q6ZRK6-1
EIF3MNM_006360.6 linkuse as main transcriptc.*440G>C 3_prime_UTR_variant 11/11 ENST00000531120.6 NP_006351.2 Q7L2H7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC73ENST00000335185.10 linkuse as main transcriptc.3212C>G p.Thr1071Arg missense_variant 18/182 NM_001008391.4 ENSP00000335325.5 Q6ZRK6-1
EIF3MENST00000531120.6 linkuse as main transcriptc.*440G>C 3_prime_UTR_variant 11/111 NM_006360.6 ENSP00000436049.1 Q7L2H7-1
CCDC73ENST00000528333.1 linkuse as main transcriptc.317C>G p.Thr106Arg missense_variant 2/23 ENSP00000434365.1 H0YDV2
EIF3MENST00000524896.5 linkuse as main transcriptc.*440G>C downstream_gene_variant 2 ENSP00000436787.1 Q7L2H7-2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151898
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1449716
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
720824
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151898
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74174
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.00000756

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 GeneticsDec 18, 2023The c.3212C>G (p.T1071R) alteration is located in exon 18 (coding exon 17) of the CCDC73 gene. This alteration results from a C to G substitution at nucleotide position 3212, causing the threonine (T) at amino acid position 1071 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
15
DANN
Benign
0.91
DEOGEN2
Benign
0.0036
T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.037
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.27
N
REVEL
Benign
0.10
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.022
D
Polyphen
0.0010
B
Vest4
0.20
MutPred
0.26
Loss of phosphorylation at T1071 (P = 0.0158);
MVP
0.061
MPC
0.17
ClinPred
0.12
T
GERP RS
4.3
Varity_R
0.16
gMVP
0.17

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

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

Other links and lift over

dbSNP: rs186329131; hg19: chr11-32624385; API