11-32602840-T-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.3211A>Gā€‹(p.Thr1071Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,326 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: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CCDC73
NM_001008391.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.233
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=0.03754145).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC73NM_001008391.4 linkuse as main transcriptc.3211A>G p.Thr1071Ala missense_variant 18/18 ENST00000335185.10 NP_001008392.2 Q6ZRK6-1
EIF3MNM_006360.6 linkuse as main transcriptc.*441T>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.3211A>G p.Thr1071Ala missense_variant 18/182 NM_001008391.4 ENSP00000335325.5 Q6ZRK6-1
EIF3MENST00000531120.6 linkuse as main transcriptc.*441T>C 3_prime_UTR_variant 11/111 NM_006360.6 ENSP00000436049.1 Q7L2H7-1
CCDC73ENST00000528333.1 linkuse as main transcriptc.316A>G p.Thr106Ala missense_variant 2/23 ENSP00000434365.1 H0YDV2
EIF3MENST00000524896.5 linkuse as main transcriptc.*441T>C downstream_gene_variant 2 ENSP00000436787.1 Q7L2H7-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1452326
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
722198
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsMay 10, 2024The c.3211A>G (p.T1071A) alteration is located in exon 18 (coding exon 17) of the CCDC73 gene. This alteration results from a A to G substitution at nucleotide position 3211, causing the threonine (T) at amino acid position 1071 to be replaced by an alanine (A). 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
0.090
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
15
DANN
Benign
0.92
DEOGEN2
Benign
0.0064
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
0.21
N
REVEL
Benign
0.032
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.085
T
Polyphen
0.0010
B
Vest4
0.15
MutPred
0.24
Loss of phosphorylation at T1071 (P = 0.0158);
MVP
0.13
MPC
0.11
ClinPred
0.086
T
GERP RS
3.0
Varity_R
0.072
gMVP
0.064

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: chr11-32624386; API