chr22-28786274-T-C

Position:

• chr22-28786274-T-C

Variant summary

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

The NM_173510.4(CCDC117):​c.788T>C​(p.Leu263Pro) 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: 32)
• Consequence: CCDC117 NM_173510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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=0.07961607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC117	NM_173510.4	c.788T>C	p.Leu263Pro	missense_variant	5/5	ENST00000249064.9
CCDC117	NM_001284263.2	c.734T>C	p.Leu245Pro	missense_variant	4/4
CCDC117	NM_001284264.2	c.563T>C	p.Leu188Pro	missense_variant	4/4
CCDC117	NM_001284265.1	c.392T>C	p.Leu131Pro	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC117	ENST00000249064.9	c.788T>C	p.Leu263Pro	missense_variant	5/5	1	NM_173510.4	P1
CCDC117	ENST00000448492.6	c.734T>C	p.Leu245Pro	missense_variant	4/4	2
CCDC117	ENST00000421503.6	c.563T>C	p.Leu188Pro	missense_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 08, 2022

The c.788T>C (p.L263P) alteration is located in exon 5 (coding exon 5) of the CCDC117 gene. This alteration results from a T to C substitution at nucleotide position 788, causing the leucine (L) at amino acid position 263 to be replaced by a proline (P). 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	0.081
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.13
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.091
MutPred		0.14		Gain of loop (P = 0.0435);.;.;
MVP		0.10
MPC		0.0081
ClinPred		0.16	T
GERP RS		5.9
Varity_R		0.34
gMVP		0.28

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: chr22-29182262;