Variant 11-32602840-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008391.4(CCDC73):c.3211A>G(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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCDC73
NM_001008391.4 missense

Scores

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)

CCDC73 links:

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]

EIF3M links:

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
CCDC73	NM_001008391.4 linkuse as main transcript	c.3211A>G	p.Thr1071Ala	missense_variant	18/18	ENST00000335185.10	NP_001008392.2	Q6ZRK6-1
EIF3M	NM_006360.6 linkuse as main transcript	c.*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	UniProt
CCDC73	ENST00000335185.10 linkuse as main transcript	c.3211A>G	p.Thr1071Ala	missense_variant	18/18	2	NM_001008391.4	ENSP00000335325.5	Q6ZRK6-1
EIF3M	ENST00000531120.6 linkuse as main transcript	c.*441T>C		3_prime_UTR_variant	11/11	1	NM_006360.6	ENSP00000436049.1	Q7L2H7-1
CCDC73	ENST00000528333.1 linkuse as main transcript	c.316A>G	p.Thr106Ala	missense_variant	2/2	3		ENSP00000434365.1	H0YDV2
EIF3M	ENST00000524896.5 linkuse as main transcript	c.*441T>C		downstream_gene_variant		2		ENSP00000436787.1	Q7L2H7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452326

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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.:

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 submitter

clinical testing

Ambry Genetics

May 10, 2024

The 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

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.26

M_CAP

Benign

0.0027

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.21

REVEL

Benign

0.032

Sift

Uncertain

0.0080

Sift4G

Benign

0.085

Polyphen

0.0010

Vest4

0.15

MutPred

0.24

Loss of phosphorylation at T1071 (P = 0.0158);

MVP

0.13

MPC

0.11

ClinPred

0.086

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over