chr22-28773004-G-C

Position:

• chr22-28773004-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000249064.9(CCDC117):​c.155G>C​(p.Ser52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC117 ENST00000249064.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

CCDC117 (HGNC:26599): (coiled-coil domain containing 117)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12589419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC117	NM_173510.4	c.155G>C	p.Ser52Thr	missense_variant	1/5	ENST00000249064.9	NP_775781.1
CCDC117	NM_001284263.2	c.155G>C	p.Ser52Thr	missense_variant	1/4		NP_001271192.1
CCDC117	NM_001284264.2	c.155G>C	p.Ser52Thr	missense_variant	1/4		NP_001271193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC117	ENST00000249064.9	c.155G>C	p.Ser52Thr	missense_variant	1/5	1	NM_173510.4	ENSP00000249064	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 03, 2021

The c.155G>C (p.S52T) alteration is located in exon 1 (coding exon 1) of the CCDC117 gene. This alteration results from a G to C substitution at nucleotide position 155, causing the serine (S) at amino acid position 52 to be replaced by a threonine (T). 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	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.025	T;.;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L;.
MutationTaster	Benign	0.52	D;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.90	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.042	D;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.59	P;.;.;.
Vest4		0.15
MutPred		0.15		Gain of glycosylation at S52 (P = 0.0502);Gain of glycosylation at S52 (P = 0.0502);Gain of glycosylation at S52 (P = 0.0502);Gain of glycosylation at S52 (P = 0.0502);
MVP		0.15
MPC		0.022
ClinPred		0.51	D
GERP RS		4.2
Varity_R		0.18
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-29168992;