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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008391.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC73	NM_001008391.4	MANE Select	c.3125G>T	p.Ser1042Ile	missense	Exon 18 of 18	NP_001008392.2	Q6ZRK6-1
	EIF3M	NM_006360.6	MANE Select	c.*527C>A		3_prime_UTR	Exon 11 of 11	NP_006351.2
	EIF3M	NM_001307929.2		c.*527C>A		3_prime_UTR	Exon 8 of 8	NP_001294858.1	Q7L2H7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC73	ENST00000335185.10	TSL:2 MANE Select	c.3125G>T	p.Ser1042Ile	missense	Exon 18 of 18	ENSP00000335325.5	Q6ZRK6-1
	EIF3M	ENST00000531120.6	TSL:1 MANE Select	c.*527C>A		3_prime_UTR	Exon 11 of 11	ENSP00000436049.1	Q7L2H7-1
	CCDC73	ENST00000528333.1	TSL:3	c.230G>T	p.Ser77Ile	missense	Exon 2 of 2	ENSP00000434365.1	H0YDV2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;