19-17942742-G-T

Position:

• chr19-17942742-G-T

Variant summary

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

The NM_001136203.2(CCDC124):​c.246G>T​(p.Lys82Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC124 NM_001136203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

Genes affected

CCDC124 (HGNC:25171): (coiled-coil domain containing 124) Enables RNA binding activity. Predicted to be involved in cell division. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2704241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2	c.246G>T	p.Lys82Asn	missense_variant	3/5	ENST00000445755.7	NP_001129675.1
CCDC124	NM_138442.4	c.246G>T	p.Lys82Asn	missense_variant	3/5		NP_612451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC124	ENST00000445755.7	c.246G>T	p.Lys82Asn	missense_variant	3/5	2	NM_001136203.2	ENSP00000408730.1
CCDC124	ENST00000597436.5	c.246G>T	p.Lys82Asn	missense_variant	3/5	1		ENSP00000471455.1
CCDC124	ENST00000596123.1	c.246G>T	p.Lys82Asn	missense_variant	2/3	2		ENSP00000472520.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 27, 2024

The c.246G>T (p.K82N) alteration is located in exon 3 (coding exon 2) of the CCDC124 gene. This alteration results from a G to T substitution at nucleotide position 246, causing the lysine (K) at amino acid position 82 to be replaced by an asparagine (N). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D;.;.
REVEL	Benign	0.17
Sift	Benign	0.045	D;.;.
Sift4G	Benign	0.064	T;T;D
Polyphen		0.89	P;P;.
Vest4		0.36
MutPred		0.16		Loss of ubiquitination at K82 (P = 0.0155);Loss of ubiquitination at K82 (P = 0.0155);Loss of ubiquitination at K82 (P = 0.0155);
MVP		0.56
MPC		0.88
ClinPred		0.95	D
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.23

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: chr19-18053551;