17-81208867-A-T

Variant names:

• chr17-81208867-A-T
• rs9896314
• NM_014984.4:c.272+61T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014984.4(CEP131):​c.272+61T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000596 in 1,174,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: CEP131 NM_014984.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 5 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP131	NM_014984.4	c.272+61T>A		intron_variant	Intron 3 of 25	ENST00000450824.7	NP_055799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP131	ENST00000450824.7	c.272+61T>A		intron_variant	Intron 3 of 25	1	NM_014984.4	ENSP00000393583.2
CEP131	ENST00000269392.8	c.272+61T>A		intron_variant	Intron 3 of 25	1		ENSP00000269392.4
CEP131	ENST00000575907.5	c.272+61T>A		intron_variant	Intron 3 of 24	1		ENSP00000459733.1
CEP131	ENST00000374782.7	c.272+61T>A		intron_variant	Intron 3 of 24	5		ENSP00000363914.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000596 AC: 7 AN: 1174504 Hom.: 0 AF XY: 0.00000839 AC XY: 5 AN XY: 596208

African (AFR) AF: 0.00 AC: 0 AN: 28084

American (AMR) AF: 0.0000494 AC: 2 AN: 40494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23502

East Asian (EAS) AF: 0.00 AC: 0 AN: 37836

South Asian (SAS) AF: 0.00 AC: 0 AN: 78572

European-Finnish (FIN) AF: 0.0000201 AC: 1 AN: 49782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3744

European-Non Finnish (NFE) AF: 0.00000464 AC: 4 AN: 861658

Other (OTH) AF: 0.00 AC: 0 AN: 50832

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-2.4

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: rs9896314; hg19: chr17-79182667;