11-65891298-C-A

Variant names:

• chr11-65891298-C-A
• rs1416594855
• NM_006848.3:c.515C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006848.3(CCDC85B):​c.515C>A​(p.Pro172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P172L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCDC85B NM_006848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24117938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85B	NM_006848.3	MANE Select	c.515C>A	p.Pro172Gln	missense	Exon 1 of 1	NP_006839.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85B	ENST00000312579.4	TSL:6 MANE Select	c.515C>A	p.Pro172Gln	missense	Exon 1 of 1	ENSP00000311695.2	Q15834

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428142 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708776

African (AFR) AF: 0.0000321 AC: 1 AN: 31118

American (AMR) AF: 0.00 AC: 0 AN: 40552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 36262

South Asian (SAS) AF: 0.00 AC: 0 AN: 82438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097682

Other (OTH) AF: 0.00 AC: 0 AN: 59032

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Benign	0.027
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.076
Sift	Benign	0.090	T
Sift4G	Benign	0.36	T
Polyphen		0.99	D
Vest4		0.10
MutPred		0.39		Loss of catalytic residue at P172 (P = 0.0062)
MVP		0.72
MPC		2.6
ClinPred		0.95	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.13
gMVP		0.21
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1416594855; hg19: chr11-65658769;