11-85882540-T-C

Position:

• chr11-85882540-T-C

Variant summary

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

The NM_001286159.2(CCDC83):​c.208T>C​(p.Trp70Arg) 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. 12/21 in silico tools predict 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: 32)
• Consequence: CCDC83 NM_001286159.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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=0.360075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2	c.208T>C	p.Trp70Arg	missense_variant	4/11	ENST00000342404.8	NP_001273088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC83	ENST00000342404.8	c.208T>C	p.Trp70Arg	missense_variant	4/11	1	NM_001286159.2	ENSP00000344512.3
CCDC83	ENST00000526729.1	c.91T>C	p.Trp31Arg	missense_variant	2/8	1		ENSP00000434373.1
CCDC83	ENST00000280245.8	c.208T>C	p.Trp70Arg	missense_variant	4/12	2		ENSP00000280245.4
CCDC83	ENST00000529676.2	n.86+9245T>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 08, 2024

The c.208T>C (p.W70R) alteration is located in exon 4 (coding exon 3) of the CCDC83 gene. This alteration results from a T to C substitution at nucleotide position 208, causing the tryptophan (W) at amino acid position 70 to be replaced by an arginine (R). 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.043	.;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.24
Sift	Benign	0.089	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.33
MutPred		0.67		Gain of disorder (P = 5e-04);Gain of disorder (P = 5e-04);
MVP		0.14
MPC		0.059
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.19
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr11-85593583;