22-28781161-G-T

Position:

• chr22-28781161-G-T

Variant summary

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

The ENST00000249064.9(CCDC117):​c.453G>T​(p.Glu151Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC117 ENST00000249064.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.494

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=0.19040057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC117	NM_173510.4	c.453G>T	p.Glu151Asp	missense_variant	3/5	ENST00000249064.9	NP_775781.1
CCDC117	NM_001284263.2	c.399G>T	p.Glu133Asp	missense_variant	2/4		NP_001271192.1
CCDC117	NM_001284265.1	c.57G>T	p.Glu19Asp	missense_variant	3/5		NP_001271194.1
CCDC117	NM_001284264.2	c.240-2347G>T		intron_variant			NP_001271193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC117	ENST00000249064.9	c.453G>T	p.Glu151Asp	missense_variant	3/5	1	NM_173510.4	ENSP00000249064	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

Oct 04, 2022

The c.453G>T (p.E151D) alteration is located in exon 3 (coding exon 3) of the CCDC117 gene. This alteration results from a G to T substitution at nucleotide position 453, causing the glutamic acid (E) at amino acid position 151 to be replaced by an aspartic acid (D). 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	0.58
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	0.74	D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.14	T;T;D
Polyphen		1.0	D;.;.
Vest4		0.67
MutPred		0.11		Gain of ubiquitination at K148 (P = 0.1092);.;.;
MVP		0.068
MPC		0.027
ClinPred		0.96	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.16

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: chr22-29177149;