22-28773730-C-T

Position:

• chr22-28773730-C-T

Variant summary

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

The NM_173510.4(CCDC117):​c.191C>T​(p.Ser64Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC117 NM_173510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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=0.2369357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC117	NM_173510.4	c.191C>T	p.Ser64Phe	missense_variant	2/5	ENST00000249064.9
CCDC117	NM_001284264.2	c.191C>T	p.Ser64Phe	missense_variant	2/4
CCDC117	NM_001284265.1	c.-206C>T		5_prime_UTR_variant	2/5
CCDC117	NM_001284263.2	c.185+696C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC117	ENST00000249064.9	c.191C>T	p.Ser64Phe	missense_variant	2/5	1	NM_173510.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 28, 2023

The c.191C>T (p.S64F) alteration is located in exon 2 (coding exon 2) of the CCDC117 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 to be replaced by a phenylalanine (F). 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	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	0.91	D;D;D;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.13
Sift	Benign	0.29	T;D
Sift4G	Benign	1.0	T;T
Polyphen		0.010	B;.
Vest4		0.58
MutPred		0.37		Loss of phosphorylation at S64 (P = 0.0103);Loss of phosphorylation at S64 (P = 0.0103);
MVP		0.13
MPC		0.0079
ClinPred		0.10	T
GERP RS		3.9
Varity_R		0.081
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2031070808; hg19: chr22-29169718;