11-85912671-C-G

Position:

• chr11-85912671-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286159.2(CCDC83):​c.794+1269C>G variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC83 NM_001286159.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056758642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2	c.794+1269C>G		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+1269C>G		intron_variant		1	NM_001286159.2	ENSP00000344512	P1
CCDC83	ENST00000526729.1	c.511+1269C>G		intron_variant		1		ENSP00000434373
CCDC83	ENST00000280245.8	c.817C>G	p.Pro273Ala	missense_variant	9/12	2		ENSP00000280245
CCDC83	ENST00000529676.2	n.369+1269C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jun 06, 2023

The c.817C>G (p.P273A) alteration is located in exon 9 (coding exon 8) of the CCDC83 gene. This alteration results from a C to G substitution at nucleotide position 817, causing the proline (P) at amino acid position 273 to be replaced by an alanine (A). 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	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.4
DANN	Uncertain	0.98
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.0030
Sift	Benign	0.13	T
Sift4G	Benign	1.0	T
Polyphen		0.034	B
Vest4		0.29
MutPred		0.24		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.061
MPC		0.023
ClinPred		0.079	T
GERP RS		0.24
gMVP		0.024

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: chr11-85623714;