17-81189922-T-A

Position:

• chr17-81189922-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014984.4(CEP131):​c.3161A>T​(p.Gln1054Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CEP131 NM_014984.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37285793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP131	NM_014984.4	c.3161A>T	p.Gln1054Leu	missense_variant	25/26	ENST00000450824.7	NP_055799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP131	ENST00000450824.7	c.3161A>T	p.Gln1054Leu	missense_variant	25/26	1	NM_014984.4	ENSP00000393583.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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 19, 2024

The c.3161A>T (p.Q1054L) alteration is located in exon 25 (coding exon 24) of the CEP131 gene. This alteration results from a A to T substitution at nucleotide position 3161, causing the glutamine (Q) at amino acid position 1054 to be replaced by a leucine (L). 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	0.25
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	.;T;.;.;.
Eigen	Benign	0.0057
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.3	D;D;.;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D;.;D;.
Sift4G	Uncertain	0.036	D;D;T;D;D
Polyphen		0.87	P;P;.;B;.
Vest4		0.73
MutPred		0.13		.;Loss of MoRF binding (P = 0.112);.;.;.;
MVP		0.45
MPC		0.20
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.49
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1482888347; hg19: chr17-79163722;