chr17-81208978-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP131	NM_014984.4	c.222A>T	p.Arg74Ser	missense_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>T	p.Arg74Ser	missense_variant	Exon 3 of 26	1	NM_014984.4	ENSP00000393583.2
CEP131	ENST00000269392.8	c.222A>T	p.Arg74Ser	missense_variant	Exon 3 of 26	1		ENSP00000269392.4
CEP131	ENST00000575907.5	c.222A>T	p.Arg74Ser	missense_variant	Exon 3 of 25	1		ENSP00000459733.1
CEP131	ENST00000374782.7	c.222A>T	p.Arg74Ser	missense_variant	Exon 3 of 25	5		ENSP00000363914.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.7	D;D;D;.
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Benign	0.083	T;T;T;T
Polyphen		0.57	P;B;D;.
Vest4		0.79
MutPred		0.34		Loss of MoRF binding (P = 0.0287);Loss of MoRF binding (P = 0.0287);Loss of MoRF binding (P = 0.0287);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

Publications

LitVar

Other links and lift over

dbSNP: rs62075318; hg19: chr17-79182778;