17-63754439-A-T

Position:

• chr17-63754439-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020198.3(CCDC47):​c.1028T>A​(p.Met343Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC47 NM_020198.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36695784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC47	NM_020198.3	c.1028T>A	p.Met343Lys	missense_variant	9/13	ENST00000225726.10	NP_064583.2
CCDC47	XM_005257527.3	c.1028T>A	p.Met343Lys	missense_variant	9/13		XP_005257584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC47	ENST00000225726.10	c.1028T>A	p.Met343Lys	missense_variant	9/13	1	NM_020198.3	ENSP00000225726.5
CCDC47	ENST00000403162.7	c.1028T>A	p.Met343Lys	missense_variant	10/14	2		ENSP00000384888.3
CCDC47	ENST00000582252.1	c.1028T>A	p.Met343Lys	missense_variant	9/12	2		ENSP00000463577.1
CCDC47	ENST00000582331.2	n.667T>A		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.1028T>A (p.M343K) alteration is located in exon 9 (coding exon 8) of the CCDC47 gene. This alteration results from a T to A substitution at nucleotide position 1028, causing the methionine (M) at amino acid position 343 to be replaced by a lysine (K). 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	0.68
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.086	T;T;T;.
Eigen	Benign	-0.095
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	.;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L;.;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.17	N;N;.;.
REVEL	Uncertain	0.33
Sift	Benign	0.92	T;T;.;.
Sift4G	Benign	0.92	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.71
MutPred		0.54		Gain of ubiquitination at M343 (P = 0.0039);Gain of ubiquitination at M343 (P = 0.0039);.;Gain of ubiquitination at M343 (P = 0.0039);
MVP		0.67
MPC		0.38
ClinPred		0.78	D
GERP RS		6.0
Varity_R		0.40
gMVP		0.74

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: chr17-61831799;