22-21634320-C-T

Variant names:

• chr22-21634320-C-T
• NM_152612.3:c.371C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152612.3(CCDC116):​c.371C>T​(p.Ala124Val) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC116 NM_152612.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• Publications: 0 publications found

Genes affected

CCDC116 (HGNC:26688): (coiled-coil domain containing 116) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037243158).
• BP6: Variant 22-21634320-C-T is Benign according to our data. Variant chr22-21634320-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2263556.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC116	NM_152612.3	c.371C>T	p.Ala124Val	missense_variant	Exon 3 of 5	ENST00000292779.4	NP_689825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC116	ENST00000292779.4	c.371C>T	p.Ala124Val	missense_variant	Exon 3 of 5	1	NM_152612.3	ENSP00000292779.3
CCDC116	ENST00000607942.5	c.371C>T	p.Ala124Val	missense_variant	Exon 3 of 4	2		ENSP00000476296.1
CCDC116	ENST00000425975.1	c.*111C>T		downstream_gene_variant		4		ENSP00000401637.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 03, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.10
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.27
DANN	Benign	0.97
DEOGEN2	Benign	0.0029	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.090	N;N
PhyloP100		-1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	.;N
REVEL	Benign	0.0060
Sift	Benign	0.57	.;T
Sift4G	Benign	0.26	T;T
Vest4		0.051
MutPred		0.10		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.099
MPC		0.21
ClinPred		0.097	T
GERP RS		-6.0
Varity_R		0.029
gMVP		0.043
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr22-21988609;