Variant 17-63752777-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020198.3(CCDC47):c.1057C>T(p.Pro353Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CCDC47
NM_020198.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.66

Variant links:

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 links:

CCDC47 (HGNC:):

CCDC47 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC47	NM_020198.3 linkuse as main transcript	c.1057C>T	p.Pro353Ser	missense_variant	10/13	ENST00000225726.10	NP_064583.2	Q96A33-1
CCDC47	XM_005257527.3 linkuse as main transcript	c.1057C>T	p.Pro353Ser	missense_variant	10/13		XP_005257584.1	Q96A33-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC47	ENST00000225726.10 linkuse as main transcript	c.1057C>T	p.Pro353Ser	missense_variant	10/13	1	NM_020198.3	ENSP00000225726.5	Q96A33-1
CCDC47	ENST00000403162.7 linkuse as main transcript	c.1057C>T	p.Pro353Ser	missense_variant	11/14	2		ENSP00000384888.3	Q96A33-1
CCDC47	ENST00000582252.1 linkuse as main transcript	c.1057C>T	p.Pro353Ser	missense_variant	10/12	2		ENSP00000463577.1	Q96A33-2
CCDC47	ENST00000582331.2 linkuse as main transcript	n.*3C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 10, 2022

The c.1057C>T (p.P353S) alteration is located in exon 10 (coding exon 9) of the CCDC47 gene. This alteration results from a C to T substitution at nucleotide position 1057, causing the proline (P) at amino acid position 353 to be replaced by a serine (S). 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

0.92

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Uncertain

0.69

D;D;T;.

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.90

D;D;D;D

MetaSVM

Uncertain

0.022

MutationAssessor

Uncertain

2.6

M;M;.;M

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.7

D;D;.;.

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0050

D;D;.;.

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.68

MutPred

0.76

Loss of glycosylation at P353 (P = 0.0674);Loss of glycosylation at P353 (P = 0.0674);.;Loss of glycosylation at P353 (P = 0.0674);

MVP

0.92

MPC

0.90

ClinPred

0.95

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.53

gMVP

0.67

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

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