chr10-12898592-G-A

Variant names:

• chr10-12898592-G-A
• rs767395696
• NM_031455.4:c.637C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_031455.4(CCDC3):​c.637C>T​(p.Arg213Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,614,084 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (2 hom.)
• Consequence: CCDC3 NM_031455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• Publications: 1 publications found

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]

ENSG00000285520 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16960487).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031455.4. 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
	CCDC3	NM_031455.4	MANE Select	c.637C>T	p.Arg213Cys	missense	Exon 3 of 3	NP_113643.1	Q9BQI4-1
	CCDC3	NM_001282658.2		c.262C>T	p.Arg88Cys	missense	Exon 7 of 7	NP_001269587.1	Q9BQI4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC3	ENST00000378825.5	TSL:1 MANE Select	c.637C>T	p.Arg213Cys	missense	Exon 3 of 3	ENSP00000368102.3	Q9BQI4-1
	CCDC3	ENST00000870347.1		c.616C>T	p.Arg206Cys	missense	Exon 3 of 3	ENSP00000540406.1
	CCDC3	ENST00000378839.1	TSL:2	c.262C>T	p.Arg88Cys	missense	Exon 7 of 7	ENSP00000368116.1	Q9BQI4-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251412 AF XY: 0.0000809

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000499 AC: 73 AN: 1461892 Hom.: 2 Cov.: 35 AF XY: 0.0000688 AC XY: 50 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112012

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.20		Gain of methylation at K212 (P = 0.0147)
MVP		0.11
MPC		0.56
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.46
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: rs767395696; hg19: chr10-12940592;