17-81208980-T-G

Variant names:

• chr17-81208980-T-G
• NM_014984.4:c.220A>C
• CEP131 p.Arg74Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014984.4(CEP131):​c.220A>C​(p.Arg74Arg) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP131 NM_014984.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

Genes affected

CEP131 (HGNC:29511): (centrosomal protein 131) Enables protein homodimerization activity. Involved in several processes, including intraciliary transport involved in cilium assembly; protein localization to centrosome; and regulation of centrosome duplication. Located in several cellular components, including ciliary transition zone; intercellular bridge; and microtubule organizing center. Colocalizes with centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CEP131 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=2.52 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014984.4. 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
	CEP131	NM_014984.4	MANE Select	c.220A>C	p.Arg74Arg	synonymous	Exon 3 of 26	NP_055799.2	Q9UPN4-2
	CEP131	NM_001319228.2		c.220A>C	p.Arg74Arg	synonymous	Exon 3 of 26	NP_001306157.1	Q9UPN4-1
	CEP131	NM_001319229.2		c.220A>C	p.Arg74Arg	synonymous	Exon 3 of 25	NP_001306158.1	I3L2J8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP131	ENST00000450824.7	TSL:1 MANE Select	c.220A>C	p.Arg74Arg	synonymous	Exon 3 of 26	ENSP00000393583.2	Q9UPN4-2
	CEP131	ENST00000269392.8	TSL:1	c.220A>C	p.Arg74Arg	synonymous	Exon 3 of 26	ENSP00000269392.4	Q9UPN4-1
	CEP131	ENST00000575907.5	TSL:1	c.220A>C	p.Arg74Arg	synonymous	Exon 3 of 25	ENSP00000459733.1	I3L2J8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.44
PhyloP100		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr17-79182780;