11-96359112-A-G

Position:

• chr11-96359112-A-G

Variant summary

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

The NM_024725.4(CCDC82):​c.1447T>C​(p.Phe483Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC82 NM_024725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

CCDC82 (HGNC:26282): (coiled-coil domain containing 82) Predicted to be active in nucleus. [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/exons	MANE	Protein	UniProt
CCDC82	NM_024725.4	c.1447T>C	p.Phe483Leu	missense_variant	9/10	ENST00000646818.2	NP_079001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC82	ENST00000646818.2	c.1447T>C	p.Phe483Leu	missense_variant	9/10		NM_024725.4	ENSP00000496393

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451492 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 16, 2021

The c.1447T>C (p.F483L) alteration is located in exon 9 (coding exon 6) of the CCDC82 gene. This alteration results from a T to C substitution at nucleotide position 1447, causing the phenylalanine (F) at amino acid position 483 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T;T;T;T;T;T;T;.;.;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	.;.;.;.;.;.;.;D;T;D
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M;M;M;M;M;M;.;.;M
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.5	D;.;.;.;.;.;.;.;.;D
REVEL	Benign	0.22
Sift	Uncertain	0.024	D;.;.;.;.;.;.;.;.;D
Sift4G	Uncertain	0.024	D;.;.;.;.;.;.;.;.;D
Polyphen		0.055	B;B;B;B;B;B;B;.;.;B
Vest4		0.72
MutPred		0.70		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);.;Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP		0.26
MPC		0.082
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.37
gMVP		0.53

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: chr11-96092276;