13-43859892-T-C

Position:

• chr13-43859892-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144974.5(CCDC122):​c.335A>G​(p.Glu112Gly) 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: 33)
• Consequence: CCDC122 NM_144974.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

Genes affected

CCDC122 (HGNC:26478): (coiled-coil domain containing 122) This gene encodes a protein that contains a coiled-coil domain. Naturally occurring mutations in this gene are associated with leprosy. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41673794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC122	NM_144974.5	c.335A>G	p.Glu112Gly	missense_variant	5/7	ENST00000444614.8	NP_659411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC122	ENST00000444614.8	c.335A>G	p.Glu112Gly	missense_variant	5/7	5	NM_144974.5	ENSP00000407763	P1
CCDC122	ENST00000470137.5	n.264A>G		non_coding_transcript_exon_variant	2/4	5
CCDC122	ENST00000476570.2	n.595A>G		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 16, 2021

The c.335A>G (p.E112G) alteration is located in exon 5 (coding exon 3) of the CCDC122 gene. This alteration results from a A to G substitution at nucleotide position 335, causing the glutamic acid (E) at amino acid position 112 to be replaced by a glycine (G). 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	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.80	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.17
Sift	Benign	0.29	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	P
Vest4		0.47
MutPred		0.33		Gain of helix (P = 6e-04);
MVP		0.54
MPC		0.20
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-44434028;