17-63752357-GA-G

Position:

• chr17-63752357-GA-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_020198.3(CCDC47):​c.1165delT​(p.Ser389fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC47 NM_020198.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 5.10

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-63752357-GA-G is Pathogenic according to our data. Variant chr17-63752357-GA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 562185.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-63752357-GA-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC47	NM_020198.3	c.1165delT	p.Ser389fs	frameshift_variant	11/13	ENST00000225726.10	NP_064583.2
CCDC47	XM_005257527.3	c.1165delT	p.Ser389fs	frameshift_variant	11/13		XP_005257584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC47	ENST00000225726.10	c.1165delT	p.Ser389fs	frameshift_variant	11/13	1	NM_020198.3	ENSP00000225726.5
CCDC47	ENST00000403162.7	c.1165delT	p.Ser389fs	frameshift_variant	12/14	2		ENSP00000384888.3
CCDC47	ENST00000582252.1	c.1165delT	p.Ser389fs	frameshift_variant	11/12	2		ENSP00000463577.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Global developmental delay with dysmorphic features, liver dysfunction, pruritus, and woolly hair Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health

Sep 24, 2018

- -

Trichohepatoneurodevelopmental syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs1568246398; hg19: chr17-61829717;