17-63752765-T-C

Position:

• chr17-63752765-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020198.3(CCDC47):​c.1069A>G​(p.Arg357Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC47 NM_020198.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

Genes affected

CCDC47 (HGNC:24856): (coiled-coil domain containing 47) Enables protein folding chaperone and ribosome binding activity. Involved in ERAD pathway; endoplasmic reticulum calcium ion homeostasis; and protein insertion into ER membrane. Located in endoplasmic reticulum. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC47 (HGNC:):

ACMG classification

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=0.39413106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC47	NM_020198.3	c.1069A>G	p.Arg357Gly	missense_variant	10/13	ENST00000225726.10	NP_064583.2
CCDC47	XM_005257527.3	c.1069A>G	p.Arg357Gly	missense_variant	10/13		XP_005257584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC47	ENST00000225726.10	c.1069A>G	p.Arg357Gly	missense_variant	10/13	1	NM_020198.3	ENSP00000225726.5
CCDC47	ENST00000403162.7	c.1069A>G	p.Arg357Gly	missense_variant	11/14	2		ENSP00000384888.3
CCDC47	ENST00000582252.1	c.1069A>G	p.Arg357Gly	missense_variant	10/12	2		ENSP00000463577.1
CCDC47	ENST00000582331.2	n.*15A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.1069A>G (p.R357G) alteration is located in exon 10 (coding exon 9) of the CCDC47 gene. This alteration results from a A to G substitution at nucleotide position 1069, causing the arginine (R) at amino acid position 357 to be replaced by a glycine (G). 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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Uncertain	0.70	D;D;T;.
Eigen	Benign	0.085
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L;L;.;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.1	D;D;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.015	D;D;.;.
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.080	B;B;.;B
Vest4		0.54
MutPred		0.65		Gain of ubiquitination at K356 (P = 0.0401);Gain of ubiquitination at K356 (P = 0.0401);.;Gain of ubiquitination at K356 (P = 0.0401);
MVP		0.68
MPC		0.41
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.57
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61830125;