rs186329131

Variant names:

• chr11-32602839-G-A
• rs186329131
• NM_001008391.4:c.3212C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-32602839-G-A
• chr11-32602839-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001008391.4(CCDC73):​c.3212C>T​(p.Thr1071Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,601,552 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. T1071A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0060 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (78 hom.)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 6 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016584396).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.3212C>T	p.Thr1071Met	missense_variant	Exon 18 of 18	ENST00000335185.10	NP_001008392.2
EIF3M	NM_006360.6	c.*440G>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.3212C>T	p.Thr1071Met	missense_variant	Exon 18 of 18	2	NM_001008391.4	ENSP00000335325.5
EIF3M	ENST00000531120.6	c.*440G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1
CCDC73	ENST00000528333.1	c.317C>T	p.Thr106Met	missense_variant	Exon 2 of 2	3		ENSP00000434365.1
EIF3M	ENST00000524896.5	c.*440G>A		downstream_gene_variant		2		ENSP00000436787.1

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 910 AN: 151896 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00602

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00706 AC: 1674 AN: 237062 AF XY: 0.00682

Gnomad AFR exome AF: 0.000865

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.00623

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00614 AC: 8897 AN: 1449538 Hom.: 78 Cov.: 29 AF XY: 0.00601 AC XY: 4334 AN XY: 720748

African (AFR) AF: 0.000646 AC: 21 AN: 32522

American (AMR) AF: 0.00154 AC: 65 AN: 42328

Ashkenazi Jewish (ASJ) AF: 0.000233 AC: 6 AN: 25802

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39554

South Asian (SAS) AF: 0.00197 AC: 165 AN: 83682

European-Finnish (FIN) AF: 0.0380 AC: 2020 AN: 53094

Middle Eastern (MID) AF: 0.00194 AC: 11 AN: 5678

European-Non Finnish (NFE) AF: 0.00573 AC: 6348 AN: 1107100

Other (OTH) AF: 0.00433 AC: 259 AN: 59778

GnomAD4 genome AF: 0.00599 AC: 910 AN: 152014 Hom.: 4 Cov.: 32 AF XY: 0.00690 AC XY: 513 AN XY: 74300

African (AFR) AF: 0.00121 AC: 50 AN: 41482

American (AMR) AF: 0.00216 AC: 33 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4820

European-Finnish (FIN) AF: 0.0378 AC: 399 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00602 AC: 409 AN: 67954

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00441 Hom.: 1

Bravo AF: 0.00329

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.00166 AC: 6

ESP6500EA AF: 0.00677 AC: 55

ExAC AF: 0.00622 AC: 750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.1
DANN	Benign	0.55
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.8	N
PhyloP100		1.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.055
MPC		0.11
ClinPred		0.0025	T
GERP RS		4.3
Varity_R		0.015
gMVP		0.075
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: rs186329131; hg19: chr11-32624385;