chr11-32602831-T-G

Variant names:

• chr11-32602831-T-G
• rs775446427
• NM_001008391.4:c.3220A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001008391.4(CCDC73):​c.3220A>C​(p.Lys1074Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,446,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.506
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049906015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.3220A>C	p.Lys1074Gln	missense_variant	Exon 18 of 18	ENST00000335185.10	NP_001008392.2
EIF3M	NM_006360.6	c.*432T>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000531120.6	NP_006351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10	c.3220A>C	p.Lys1074Gln	missense_variant	Exon 18 of 18	2	NM_001008391.4	ENSP00000335325.5
EIF3M	ENST00000531120.6	c.*432T>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1
CCDC73	ENST00000528333.1	c.325A>C	p.Lys109Gln	missense_variant	Exon 2 of 2	3		ENSP00000434365.1
EIF3M	ENST00000524896.5	c.*432T>G		downstream_gene_variant		2		ENSP00000436787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000130 AC: 3 AN: 231460 AF XY: 0.0000159

Gnomad AFR exome AF: 0.0000677

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000221 AC: 32 AN: 1446262 Hom.: 0 Cov.: 29 AF XY: 0.0000278 AC XY: 20 AN XY: 718952

African (AFR) AF: 0.0000309 AC: 1 AN: 32330

American (AMR) AF: 0.00 AC: 0 AN: 41814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25724

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 83482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.0000271 AC: 30 AN: 1105166

Other (OTH) AF: 0.0000168 AC: 1 AN: 59578

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000830 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3220A>C (p.K1074Q) alteration is located in exon 18 (coding exon 17) of the CCDC73 gene. This alteration results from a A to C substitution at nucleotide position 3220, causing the lysine (K) at amino acid position 1074 to be replaced by a glutamine (Q). 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	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.51
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.043	D
Polyphen		0.21	B
Vest4		0.063
MutPred		0.14		Loss of MoRF binding (P = 0.025);
MVP		0.19
MPC		0.46
ClinPred		0.25	T
GERP RS		0.73
Varity_R		0.31
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs775446427; hg19: chr11-32624377;