11-86392712-G-T

Position:

• chr11-86392712-G-T

Variant summary

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

The NM_001156474.2(CCDC81):​c.470G>T​(p.Arg157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC81 NM_001156474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180

Genes affected

CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

LOC105369421 (HGNC:):

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/exons	MANE	Protein	UniProt
CCDC81	NM_001156474.2	c.470G>T	p.Arg157Ile	missense_variant	4/15	ENST00000445632.7	NP_001149946.1
CCDC81	NM_021827.5	c.286-2622G>T		intron_variant			NP_068599.3
LOC105369421	XR_007062826.1	n.81+3308C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC81	ENST00000445632.7	c.470G>T	p.Arg157Ile	missense_variant	4/15	1	NM_001156474.2	ENSP00000415528.2
CCDC81	ENST00000354755.5	c.286-2622G>T		intron_variant		2		ENSP00000346800.1
CCDC81	ENST00000531271.5	c.142-2622G>T		intron_variant		3		ENSP00000434959.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 12, 2023

The c.470G>T (p.R157I) alteration is located in exon 4 (coding exon 4) of the CCDC81 gene. This alteration results from a G to T substitution at nucleotide position 470, causing the arginine (R) at amino acid position 157 to be replaced by an isoleucine (I). 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	0.30
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.17
Sift	Benign	0.035	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.40		Loss of MoRF binding (P = 0.0177);
MVP		0.41
MPC		0.82
ClinPred		0.96	D
GERP RS		-2.7
Varity_R		0.20
gMVP		0.67

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: chr11-86103754;