NM_014984.4:c.272+61T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014984.4(CEP131):​c.272+61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,326,124 control chromosomes in the GnomAD database, including 597,395 homozygotes. 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: 𝑓 0.92 (65215 hom., cov: 31)
  • Exomes 𝑓: 0.95 (532180 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

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.272+61T>C		intron	N/A	NP_055799.2	Q9UPN4-2
	CEP131	NM_001319228.2		c.272+61T>C		intron	N/A	NP_001306157.1	Q9UPN4-1
	CEP131	NM_001319229.2		c.272+61T>C		intron	N/A	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.272+61T>C		intron	N/A	ENSP00000393583.2	Q9UPN4-2
	CEP131	ENST00000269392.8	TSL:1	c.272+61T>C		intron	N/A	ENSP00000269392.4	Q9UPN4-1
	CEP131	ENST00000575907.5	TSL:1	c.272+61T>C		intron	N/A	ENSP00000459733.1	I3L2J8

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140561 AN: 152044 Hom.: 65170 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.928

GnomAD4 exome AF: 0.952 AC: 1117166 AN: 1173962 Hom.: 532180 AF XY: 0.950 AC XY: 566126 AN XY: 595942

African (AFR) AF: 0.847 AC: 23739 AN: 28042

American (AMR) AF: 0.953 AC: 38583 AN: 40486

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 22775 AN: 23498

East Asian (EAS) AF: 0.872 AC: 32951 AN: 37808

South Asian (SAS) AF: 0.895 AC: 70289 AN: 78506

European-Finnish (FIN) AF: 0.967 AC: 48131 AN: 49774

Middle Eastern (MID) AF: 0.951 AC: 3554 AN: 3738

European-Non Finnish (NFE) AF: 0.963 AC: 829310 AN: 861296

Other (OTH) AF: 0.941 AC: 47834 AN: 50814

GnomAD4 genome AF: 0.924 AC: 140662 AN: 152162 Hom.: 65215 Cov.: 31 AF XY: 0.924 AC XY: 68760 AN XY: 74392

African (AFR) AF: 0.849 AC: 35242 AN: 41532

American (AMR) AF: 0.947 AC: 14487 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3353 AN: 3472

East Asian (EAS) AF: 0.869 AC: 4457 AN: 5126

South Asian (SAS) AF: 0.897 AC: 4322 AN: 4820

European-Finnish (FIN) AF: 0.972 AC: 10317 AN: 10614

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65396 AN: 67986

Other (OTH) AF: 0.929 AC: 1961 AN: 2112

Alfa AF: 0.939 Hom.: 8693

Bravo AF: 0.919

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.42
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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;