Variant 17-63752078-G-GGCACGGTTCTTATCTGCTTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_020198.3(CCDC47):c.1211_1232dupAAAAAGCAGATAAGAACCGTGC(p.Arg412fs) variant causes a frameshift, stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC47
NM_020198.3 frameshift, stop_gained

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.87

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:

ENSG00000125695 (HGNC:):

ENSG00000125695 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.152 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-63752078-G-GGCACGGTTCTTATCTGCTTTTT is Pathogenic according to our data. Variant chr17-63752078-G-GGCACGGTTCTTATCTGCTTTTT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1526240.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC47	NM_020198.3 linkuse as main transcript	c.1211_1232dupAAAAAGCAGATAAGAACCGTGC	p.Arg412fs	frameshift_variant, stop_gained	12/13	ENST00000225726.10	NP_064583.2	Q96A33-1
CCDC47	XM_005257527.3 linkuse as main transcript	c.1211_1232dupAAAAAGCAGATAAGAACCGTGC	p.Arg412fs	frameshift_variant, stop_gained	12/13		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.1211_1232dupAAAAAGCAGATAAGAACCGTGC	p.Arg412fs	frameshift_variant, stop_gained	12/13	1	NM_020198.3	ENSP00000225726.5	Q96A33-1
ENSG00000125695	ENST00000580553.1 linkuse as main transcript	n.-5_17dupAAAAAGCAGATAAGAACCGTGC		non_coding_transcript_exon_variant	1/12	5		ENSP00000464100.1	J3QR89
CCDC47	ENST00000403162.7 linkuse as main transcript	c.1211_1232dupAAAAAGCAGATAAGAACCGTGC	p.Arg412fs	frameshift_variant, stop_gained	13/14	2		ENSP00000384888.3	Q96A33-1
CCDC47	ENST00000582252.1 linkuse as main transcript	c.1211_1232dupAAAAAGCAGATAAGAACCGTGC	p.Arg412fs	frameshift_variant, stop_gained	12/12	2		ENSP00000463577.1	Q96A33-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251252

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Trichohepatoneurodevelopmental syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

3billion

Mar 22, 2022

Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000040). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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