17-81190772-T-C

Position:

• chr17-81190772-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014984.4(CEP131):​c.2974A>G​(p.Asn992Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CEP131 NM_014984.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0820

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12402648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP131	NM_014984.4	c.2974A>G	p.Asn992Asp	missense_variant	24/26	ENST00000450824.7	NP_055799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP131	ENST00000450824.7	c.2974A>G	p.Asn992Asp	missense_variant	24/26	1	NM_014984.4	ENSP00000393583.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.2974A>G (p.N992D) alteration is located in exon 24 (coding exon 23) of the CEP131 gene. This alteration results from a A to G substitution at nucleotide position 2974, causing the asparagine (N) at amino acid position 992 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.7
DANN	Benign	0.96
DEOGEN2	Benign	0.057	.;T;.;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.58	T;T;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	.;N;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.8	N;N;.;N;.
REVEL	Benign	0.054
Sift	Benign	0.15	T;T;.;T;.
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.0050	B;B;.;B;.
Vest4		0.18
MutPred		0.18		.;Loss of MoRF binding (P = 0.077);.;.;.;
MVP		0.24
MPC		0.10
ClinPred		0.81	D
GERP RS		0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.044

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79164572;