chr13-43859853-T-C

Position:

• chr13-43859853-T-C

Variant summary

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

The NM_144974.5(CCDC122):​c.374A>G​(p.Tyr125Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,455,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC122 NM_144974.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC122	NM_144974.5	c.374A>G	p.Tyr125Cys	missense_variant	5/7	ENST00000444614.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC122	ENST00000444614.8	c.374A>G	p.Tyr125Cys	missense_variant	5/7	5	NM_144974.5	P1
CCDC122	ENST00000470137.5	n.303A>G		non_coding_transcript_exon_variant	2/4	5
CCDC122	ENST00000476570.2	n.634A>G		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455188 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 723586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

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

Jan 16, 2024

The c.374A>G (p.Y125C) 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 374, causing the tyrosine (Y) at amino acid position 125 to be replaced by a cysteine (C). 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	0.22
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.18
Sift	Benign	0.10	T
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.44		Gain of catalytic residue at Y129 (P = 0);
MVP		0.39
MPC		0.25
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1467297916; hg19: chr13-44433989;