11-65890983-A-G

Variant names:

• chr11-65890983-A-G
• rs1467009068
• NM_006848.3:c.200A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_006848.3(CCDC85B):​c.200A>G​(p.Asn67Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000724 in 1,382,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: CCDC85B NM_006848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

Genes affected

CCDC85B (HGNC:24926): (coiled-coil domain containing 85B) Hepatitis delta virus (HDV) is a pathogenic human virus whose RNA genome and replication cycle resemble those of plant viroids. Delta-interacting protein A (DIPA), a cellular gene product, has been found to have homology to hepatitis delta virus antigen (HDAg). DIPA interacts with the viral antigen, HDAg, and can affect HDV replication in vitro. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC85B	NM_006848.3	c.200A>G	p.Asn67Ser	missense_variant	Exon 1 of 1	ENST00000312579.4	NP_006839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC85B	ENST00000312579.4	c.200A>G	p.Asn67Ser	missense_variant	Exon 1 of 1	6	NM_006848.3	ENSP00000311695.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000724 AC: 10 AN: 1382028 Hom.: 0 Cov.: 31 AF XY: 0.00000586 AC XY: 4 AN XY: 682326

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000400

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000834

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

Apr 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.200A>G (p.N67S) alteration is located in exon 1 (coding exon 1) of the CCDC85B gene. This alteration results from a A to G substitution at nucleotide position 200, causing the asparagine (N) at amino acid position 67 to be replaced by a serine (S). 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	0.32
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.62		Gain of phosphorylation at N67 (P = 0.0166);
MVP		0.72
MPC		2.4
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.76
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs1467009068; hg19: chr11-65658454;