13-43868752-T-G

Position:

• chr13-43868752-T-G

Variant summary

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

The NM_144974.5(CCDC122):​c.98A>C​(p.Gln33Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC122 NM_144974.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

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]

CCDC122 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC122	NM_144974.5	c.98A>C	p.Gln33Pro	missense_variant	4/7	ENST00000444614.8	NP_659411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC122	ENST00000444614.8	c.98A>C	p.Gln33Pro	missense_variant	4/7	5	NM_144974.5	ENSP00000407763.2
CCDC122	ENST00000476570.2	n.358A>C		non_coding_transcript_exon_variant	4/7	5
CCDC122	ENST00000470137.5	n.85+6090A>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Aug 08, 2023

The c.98A>C (p.Q33P) alteration is located in exon 4 (coding exon 2) of the CCDC122 gene. This alteration results from a A to C substitution at nucleotide position 98, causing the glutamine (Q) at amino acid position 33 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.15		Loss of MoRF binding (P = 0.0918);
MVP		0.56
MPC		0.26
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.76
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs769533052; hg19: chr13-44442888;