11-32602926-C-A

Variant names:

• chr11-32602926-C-A
• rs1331078904
• NM_001008391.4:c.3125G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008391.4(CCDC73):​c.3125G>T​(p.Ser1042Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S1042T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• 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: 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=0.13905182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.3125G>T	p.Ser1042Ile	missense_variant	Exon 18 of 18	ENST00000335185.10	NP_001008392.2
EIF3M	NM_006360.6	c.*527C>A		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.3125G>T	p.Ser1042Ile	missense_variant	Exon 18 of 18	2	NM_001008391.4	ENSP00000335325.5
EIF3M	ENST00000531120.6	c.*527C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1
CCDC73	ENST00000528333.1	c.230G>T	p.Ser77Ile	missense_variant	Exon 2 of 2	3		ENSP00000434365.1
EIF3M	ENST00000524896.5	c.*527C>A		downstream_gene_variant		2		ENSP00000436787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.84
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.071
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		0.92	P
Vest4		0.22
MutPred		0.22		Gain of helix (P = 0.0854);
MVP		0.19
MPC		0.52
ClinPred		0.52	D
GERP RS		-1.3
Varity_R		0.17
gMVP		0.21
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1331078904; hg19: chr11-32624472;