rs753950356

Variant names:

• chr17-65689178-C-A
• rs753950356
• NM_001199165.4:c.2648G>T
• CEP112 p.Arg883Leu

Your query was ambiguous. Multiple possible variants found:

• chr17-65689178-C-A
• chr17-65689178-C-T

Variant summary

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

The NM_001199165.4(CEP112):​c.2648G>T​(p.Arg883Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP112 NM_001199165.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• Publications: 0 publications found

Genes affected

CEP112 (HGNC:28514): (centrosomal protein 112) This gene encodes a coiled-coil domain containing protein that belongs to the cell division control protein 42 effector protein family. In neurons, it localizes to the cytoplasm of dendrites and is also enriched in the nucleus where it interacts with the RNA polymerase III transcriptional repressor Maf1 to regulate gamma-aminobutyric acid A receptor surface expression. In addition, the protein has been identified as a component of the human centrosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

CEP112 Gene-Disease associations (from GenCC):

• spermatogenic failure 44

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199165.4. 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
	CEP112	NM_001199165.4	MANE Select	c.2648G>T	p.Arg883Leu	missense	Exon 24 of 27	NP_001186094.1	Q8N8E3-1
	CEP112	NM_001353129.2		c.2651G>T	p.Arg884Leu	missense	Exon 24 of 27	NP_001340058.1
	CEP112	NM_001353127.2		c.2648G>T	p.Arg883Leu	missense	Exon 24 of 27	NP_001340056.1	Q8N8E3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP112	ENST00000535342.7	TSL:2 MANE Select	c.2648G>T	p.Arg883Leu	missense	Exon 24 of 27	ENSP00000442784.2	Q8N8E3-1
	CEP112	ENST00000537949.5	TSL:1	c.2522G>T	p.Arg841Leu	missense	Exon 22 of 25	ENSP00000440775.1	F5GYE8
	CEP112	ENST00000317442.12	TSL:1	c.416G>T	p.Arg139Leu	missense	Exon 4 of 7	ENSP00000320592.5	Q8N8E3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D
Sift4G	Benign	0.76	T
Varity_R		0.26
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs753950356; hg19: chr17-63685296;