chr22-28772969-G-C

Position:

• chr22-28772969-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000249064.9(CCDC117):​c.120G>C​(p.Glu40Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC117 ENST00000249064.9 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.338

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074635).
• BP6: Variant 22-28772969-G-C is Benign according to our data. Variant chr22-28772969-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2487709.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC117	NM_173510.4	c.120G>C	p.Glu40Asp	missense_variant	1/5	ENST00000249064.9	NP_775781.1
CCDC117	NM_001284263.2	c.120G>C	p.Glu40Asp	missense_variant	1/4		NP_001271192.1
CCDC117	NM_001284264.2	c.120G>C	p.Glu40Asp	missense_variant	1/4		NP_001271193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC117	ENST00000249064.9	c.120G>C	p.Glu40Asp	missense_variant	1/5	1	NM_173510.4	ENSP00000249064	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.0067	T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.14	N;N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.27	N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.73	T;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.090
MutPred		0.035		Loss of methylation at R44 (P = 0.1509);Loss of methylation at R44 (P = 0.1509);Loss of methylation at R44 (P = 0.1509);Loss of methylation at R44 (P = 0.1509);
MVP		0.068
MPC		0.0072
ClinPred		0.11	T
GERP RS		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.052
gMVP		0.073

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: chr22-29168957;