19-17943263-G-A

Position:

• chr19-17943263-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001136203.2(CCDC124):​c.352G>A​(p.Glu118Lys) variant causes a missense, splice region change. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC124 NM_001136203.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.51

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16321081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2	c.352G>A	p.Glu118Lys	missense_variant, splice_region_variant	4/5	ENST00000445755.7	NP_001129675.1
CCDC124	NM_138442.4	c.352G>A	p.Glu118Lys	missense_variant, splice_region_variant	4/5		NP_612451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC124	ENST00000445755.7	c.352G>A	p.Glu118Lys	missense_variant, splice_region_variant	4/5	2	NM_001136203.2	ENSP00000408730.1
CCDC124	ENST00000597436.5	c.352G>A	p.Glu118Lys	missense_variant, splice_region_variant	4/5	1		ENSP00000471455.1
CCDC124	ENST00000596123.1	c.352G>A	p.Glu118Lys	missense_variant, splice_region_variant	3/3	2		ENSP00000472520.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 130292 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 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

Feb 28, 2023

The c.352G>A (p.E118K) alteration is located in exon 4 (coding exon 3) of the CCDC124 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the glutamic acid (E) at amino acid position 118 to be replaced by a lysine (K). 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	0.088
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.0091	T;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.13	N;.;.
REVEL	Benign	0.041
Sift	Benign	0.33	T;.;.
Sift4G	Benign	0.31	T;T;T
Polyphen		0.017	B;B;.
Vest4		0.47
MutPred		0.41		Gain of MoRF binding (P = 0.0163);Gain of MoRF binding (P = 0.0163);Gain of MoRF binding (P = 0.0163);
MVP		0.35
MPC		0.39
ClinPred		0.81	D
GERP RS		3.5
Varity_R		0.10
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1384214143; hg19: chr19-18054072;