17-81208978-T-C

Variant names:

• chr17-81208978-T-C
• rs62075318
• NM_014984.4:c.222A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014984.4(CEP131):​c.222A>G​(p.Arg74Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,612,972 control chromosomes in the GnomAD database, including 179,919 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 0.38 (13875 hom., cov: 32)
  • Exomes 𝑓: 0.47 (166044 hom.)
• Consequence: CEP131 NM_014984.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815
• Publications: 15 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.815 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP131	NM_014984.4	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 26	ENST00000450824.7	NP_055799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP131	ENST00000450824.7	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 26	1	NM_014984.4	ENSP00000393583.2
CEP131	ENST00000269392.8	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 26	1		ENSP00000269392.4
CEP131	ENST00000575907.5	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 25	1		ENSP00000459733.1
CEP131	ENST00000374782.7	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 25	5		ENSP00000363914.3

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58196 AN: 151856 Hom.: 13865 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.401

GnomAD2 exomes AF: 0.503 AC: 125608 AN: 249564 AF XY: 0.504

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.571

Gnomad EAS exome AF: 0.654

Gnomad FIN exome AF: 0.505

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.483

GnomAD4 exome AF: 0.469 AC: 684529 AN: 1460998 Hom.: 166044 Cov.: 46 AF XY: 0.471 AC XY: 342411 AN XY: 726838

African (AFR) AF: 0.0754 AC: 2524 AN: 33474

American (AMR) AF: 0.676 AC: 30183 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 14834 AN: 26122

East Asian (EAS) AF: 0.647 AC: 25658 AN: 39686

South Asian (SAS) AF: 0.551 AC: 47515 AN: 86224

European-Finnish (FIN) AF: 0.499 AC: 26626 AN: 53316

Middle Eastern (MID) AF: 0.464 AC: 2660 AN: 5738

European-Non Finnish (NFE) AF: 0.456 AC: 506823 AN: 1111444

Other (OTH) AF: 0.459 AC: 27706 AN: 60336

GnomAD4 genome AF: 0.383 AC: 58210 AN: 151974 Hom.: 13875 Cov.: 32 AF XY: 0.393 AC XY: 29192 AN XY: 74278

African (AFR) AF: 0.0909 AC: 3772 AN: 41474

American (AMR) AF: 0.556 AC: 8500 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3468

East Asian (EAS) AF: 0.634 AC: 3255 AN: 5136

South Asian (SAS) AF: 0.557 AC: 2680 AN: 4814

European-Finnish (FIN) AF: 0.525 AC: 5559 AN: 10582

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31226 AN: 67898

Other (OTH) AF: 0.404 AC: 853 AN: 2114

Alfa AF: 0.420 Hom.: 7622

Bravo AF: 0.374

Asia WGS AF: 0.574 AC: 1995 AN: 3478

EpiCase AF: 0.468

EpiControl AF: 0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.81
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: rs62075318; hg19: chr17-79182778; COSMIC: COSV53954834; COSMIC: COSV53954834;