rs62075318

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-81208978-T-A
• chr17-81208978-T-C

Variant summary

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

The NM_014984.4(CEP131):​c.222A>T​(p.Arg74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP131 NM_014984.4 missense
• 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: 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_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.222A>T	p.Arg74Ser	missense	Exon 3 of 26	NP_055799.2	Q9UPN4-2
	CEP131	NM_001319228.2		c.222A>T	p.Arg74Ser	missense	Exon 3 of 26	NP_001306157.1	Q9UPN4-1
	CEP131	NM_001319229.2		c.222A>T	p.Arg74Ser	missense	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.222A>T	p.Arg74Ser	missense	Exon 3 of 26	ENSP00000393583.2	Q9UPN4-2
	CEP131	ENST00000269392.8	TSL:1	c.222A>T	p.Arg74Ser	missense	Exon 3 of 26	ENSP00000269392.4	Q9UPN4-1
	CEP131	ENST00000575907.5	TSL:1	c.222A>T	p.Arg74Ser	missense	Exon 3 of 25	ENSP00000459733.1	I3L2J8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.79
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.063	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.81
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.083	T
Polyphen		0.57	P
Vest4		0.79
MutPred		0.34		Loss of MoRF binding (P = 0.0287)
MVP		0.099
MPC		0.16
ClinPred		0.63	D
GERP RS		-9.5
Varity_R		0.66
gMVP		0.51

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

Other links and lift over

dbSNP: rs62075318; hg19: chr17-79182778;