17-63756495-G-C

Variant names:

• chr17-63756495-G-C
• NM_020198.3:c.811C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020198.3(CCDC47):​c.811C>G​(p.Arg271Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC47 NM_020198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC47	NM_020198.3	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 13	ENST00000225726.10	NP_064583.2
CCDC47	XM_005257527.3	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 13		XP_005257584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC47	ENST00000225726.10	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 13	1	NM_020198.3	ENSP00000225726.5
CCDC47	ENST00000403162.7	c.811C>G	p.Arg271Gly	missense_variant	Exon 8 of 14	2		ENSP00000384888.3
CCDC47	ENST00000582252.1	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 12	2		ENSP00000463577.1
CCDC47	ENST00000582331.2	n.450C>G		non_coding_transcript_exon_variant	Exon 3 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461314 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726972

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.63	D;D;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.4	D;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.014	D;D;.
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.90	P;P;P
Vest4		0.82
MutPred		0.54		Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);
MVP		0.70
MPC		0.89
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-61833855;