11-85912696-T-C

Position:

• chr11-85912696-T-C

Variant summary

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

The NM_173556.5(CCDC83):​c.842T>C​(p.Leu281Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CCDC83 NM_173556.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0350

Genes affected

CCDC83 (HGNC:28535): (coiled-coil domain containing 83)

CCDC83 (HGNC:):

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=0.30621266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2	c.794+1294T>C		intron_variant		ENST00000342404.8	NP_001273088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC83	ENST00000342404.8	c.794+1294T>C		intron_variant		1	NM_001286159.2	ENSP00000344512.3
CCDC83	ENST00000526729.1	c.509+1294T>C		intron_variant		1		ENSP00000434373.1
CCDC83	ENST00000280245.8	c.842T>C	p.Leu281Pro	missense_variant	9/12	2		ENSP00000280245.4
CCDC83	ENST00000529676.2	n.369+1294T>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460466 Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4 AN XY: 726656

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: 0.00000990

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 07, 2021

The c.842T>C (p.L281P) alteration is located in exon 9 (coding exon 8) of the CCDC83 gene. This alteration results from a T to C substitution at nucleotide position 842, causing the leucine (L) at amino acid position 281 to be replaced by a proline (P). 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
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.1
DANN	Uncertain	0.99
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.082
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.52		Gain of loop (P = 0.0097);
MVP		0.30
MPC		0.043
ClinPred		0.92	D
GERP RS		2.0
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2093460396; hg19: chr11-85623739;