Genetic Variant NM_001008391.4:c.3218A>T (chr11-32602833-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008391.4(CCDC73):c.3218A>T(p.Glu1073Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1073G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC73
NM_001008391.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12803543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4 link	c.3218A>T	p.Glu1073Val	missense_variant	Exon 18 of 18	ENST00000335185.10	NP_001008392.2	Q6ZRK6-1
EIF3M	NM_006360.6 link	c.*434T>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000531120.6	NP_006351.2	Q7L2H7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC73	ENST00000335185.10 link	c.3218A>T	p.Glu1073Val	missense_variant	Exon 18 of 18	2	NM_001008391.4	ENSP00000335325.5	Q6ZRK6-1
EIF3M	ENST00000531120.6 link	c.*434T>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1	Q7L2H7-1
CCDC73	ENST00000528333.1 link	c.323A>T	p.Glu108Val	missense_variant	Exon 2 of 2	3		ENSP00000434365.1	H0YDV2
EIF3M	ENST00000524896.5 link	c.*434T>A		downstream_gene_variant		2		ENSP00000436787.1	Q7L2H7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447630

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32390

American (AMR)

AF:

0.00

AC:

AN:

42018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25736

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39558

South Asian (SAS)

AF:

0.00

AC:

AN:

83640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105966

Other (OTH)

AF:

0.00

AC:

AN:

59634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.38

M_CAP

Benign

0.0035

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Benign

0.18

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.18

MutPred

0.12

Gain of methylation at K1074 (P = 0.0346);

MVP

0.13

MPC

0.37

ClinPred

0.46

GERP RS

2.0

Varity_R

0.11

gMVP

0.14

Mutation Taster

=93/7

polymorphism

(source)

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

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NM_001008391.4:c.3218A>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over