Genetic Variant CCDC47:p.Arg271Gly (chr17-63756495-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.18

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

trichohepatoneurodevelopmental syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

CCDC47 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 link	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 13	ENST00000225726.10	NP_064583.2	Q96A33-1
CCDC47	XM_005257527.3 link	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 13		XP_005257584.1	Q96A33-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC47	ENST00000225726.10 link	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 13	1	NM_020198.3	ENSP00000225726.5	Q96A33-1
CCDC47	ENST00000403162.7 link	c.811C>G	p.Arg271Gly	missense_variant	Exon 8 of 14	2		ENSP00000384888.3	Q96A33-1
CCDC47	ENST00000582252.1 link	c.811C>G	p.Arg271Gly	missense_variant	Exon 7 of 12	2		ENSP00000463577.1	Q96A33-2
CCDC47	ENST00000582331.2 link	n.450C>G		non_coding_transcript_exon_variant	Exon 3 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461314

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111494

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.63

D;D;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.0061

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.2

M;M;M

PhyloP100

3.2

PrimateAI

Uncertain

0.77

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

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over