Genetic Variant CCDC85B:p.Ser199Phe (chr11-65891379-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006848.3(CCDC85B):c.596C>T(p.Ser199Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,428,088 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CCDC85B
NM_006848.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Variant links:

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]

CCDC85B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3198179).

BS2

High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC85B	NM_006848.3 link	c.596C>T	p.Ser199Phe	missense_variant	Exon 1 of 1	ENST00000312579.4	NP_006839.2	Q15834

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC85B	ENST00000312579.4 link	c.596C>T	p.Ser199Phe	missense_variant	Exon 1 of 1	6	NM_006848.3	ENSP00000311695.2		Q15834

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000480

AC:

AN:

208364

Hom.:

AF XY:

0.00

AC XY:

AN XY:

115736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1428088

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

710466

show subpopulations

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:

0.0000264

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.596C>T (p.S199F) alteration is located in exon 1 (coding exon 1) of the CCDC85B gene. This alteration results from a C to T substitution at nucleotide position 596, causing the serine (S) at amino acid position 199 to be replaced by a phenylalanine (F). 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

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

M_CAP

Benign

0.034

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.8

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.016

Polyphen

0.98

Vest4

0.33

MutPred

0.29

Loss of phosphorylation at S199 (P = 0.0188);

MVP

0.52

MPC

2.7

ClinPred

0.85

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over