Variant 10-12898457-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000378825.5(CCDC3):c.772A>C(p.Asn258His) variant causes a missense change. 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC3
ENST00000378825.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

CCDC3 (HGNC:23813): (coiled-coil domain containing 3) Involved in negative regulation of gene expression; negative regulation of lipid metabolic process; and negative regulation of tumor necrosis factor-mediated signaling pathway. Located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CCDC3 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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=0.30221787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC3	NM_031455.4 linkuse as main transcript	c.772A>C	p.Asn258His	missense_variant	3/3	ENST00000378825.5	NP_113643.1
CCDC3	NM_001282658.2 linkuse as main transcript	c.397A>C	p.Asn133His	missense_variant	7/7		NP_001269587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC3	ENST00000378825.5 linkuse as main transcript	c.772A>C	p.Asn258His	missense_variant	3/3	1	NM_031455.4	ENSP00000368102	P1	Q9BQI4-1
	ENST00000649832.1 linkuse as main transcript	n.511-55T>G		intron_variant, non_coding_transcript_variant
CCDC3	ENST00000378839.1 linkuse as main transcript	c.397A>C	p.Asn133His	missense_variant	7/7	2		ENSP00000368116		Q9BQI4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1458562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725138

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:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.772A>C (p.N258H) alteration is located in exon 3 (coding exon 3) of the CCDC3 gene. This alteration results from a A to C substitution at nucleotide position 772, causing the asparagine (N) at amino acid position 258 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.59

T;T

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.99

D;.

Vest4

0.45

MutPred

0.11

Loss of MoRF binding (P = 0.1267);.;

MVP

0.081

MPC

0.49

ClinPred

0.98

GERP RS

5.2

Varity_R

0.16

gMVP

0.24

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